- Total Synthesis and Cytotoxic Activity of 6,8-Dimethoxy-1,3-dimethylisoquinoline Isolated from Ancistrocladus tectorius: A 6π-Azaelectrocyclization Approach
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A facile and convenient approach toward the total synthesis of 1,3-dimethyl-6,8-dimethoxyisoquinoline from phloroacetophenone is reported. The sequence entailed the selective 2,4-di-O-methylation and further triflation of the resulting phenolic product. This was followed by a Stille-type allylation, an allyl-to-propenyl isomerization, and the methoximation of the carbonyl moiety. A final microwave-assisted 6π-azaelectrocyclization completed the sequence. Functionalized derivatives on C-1 were also prepared. The heterocycles exhibited cytotoxic activity.
- Cortés, Iván,Borini Etichetti, Carla M.,Girardini, Javier E.,Kaufman, Teodoro S.,Bracca, Andrea B. J.
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Read Online
- Dual inhibitors of Interleukin-6 and acetylcholinesterase for treatment of Alzheimer's disease: Design, docking, synthesis and biological evaluation
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Multitarget compounds intercept two or more functionally complementary pathways simultaneously, and are therefore considered to have potential in effectively treating complex multifactorial diseases like Alzheimer's disease (AD). In the present study, novel molecules are designed by coupling a chromone and a N,N-disubstituted carbamoyl amine as pharmacophore for interleukin-6 (IL-6) and acetylcholinesterase (AChE) inhibition, respectively. Four series (Y1–Y4) of 40 compounds are designed by using alkyl linkers of different lengths (1–4 carbon atoms) for the coupling of the two selected pharmacophore. Docking of all designed compounds in AChE leads to the identification of twelve best fit compounds (Docking score >8.3). The data suggests that a 1- or 2-carbon atom linker is the most conducive to orient the pharmacophore for optimum binding with AChE active site. The predicted ADME properties of the 12 selected compounds suggest that these can cross the blood brain barrier (BBB) with good oral bioavailability. These compounds are synthesised and evaluated for anti-AChE activity. Five compounds, showing >45% inhibition of AChE, are further evaluated for IL-6 inhibitory activity. Compound Y1f is found to be the most potent inhibitor of both AChE and IL-6 (IC50 0.7 and 0.8 ?μM, respectively). It suggests that a chromone moiety connected to a piperidine ring through a 1-carbon atom linker may provide a useful template to medical chemists for the development of new chemical entities effective against AD.
- Bansal, Yogita,Kaur, Sukhvir
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- Total Synthesis of Mulberry Diels-Alder-Type Adducts Kuwanons G and H
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Mulberry Diels-Alder-type adducts (MDAAs) are a group of rare natural polyphenols biosynthetically derived from [4 + 2]-cycloaddition of chalcones and dehydroprenylphenols. In this study, kuwanons G (1) and H (2), two bioactive MDAAs with unique dehydroprenylflavonoid dienes, were totally synthesized for the first time in a biomimetic manner. The key features of the convergent route include the use of the Baker-Venkataraman rearrangement, alkylation of β-diketone, intramolecular cyclization, and Suzuki-Miyaura coupling to achieve the subunit diene.
- Luo, Si-Yuan,Tang, Zhuo-Ya,Li, Qingjiang,Weng, Jiang,Yin, Sheng,Tang, Gui-Hua
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p. 4786 - 4793
(2021/04/06)
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- The first synthesis of podocarflavone A and its analogs and evaluation of their antimycobacterial potential against Mycobacterium tuberculosis with the support of virtual screening
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The first synthetic route developed for Podocarflavone A reported from Podocarpus macrophyllus and its analogs in 7 steps. Computational analysis for binding with the pantothenate kinase (3AVO) of Mycobacterium tuberculosis showed their docking score (ds) in the range of ?8.9 to ?9.3 Kcal/mol. MD simulations delineated the stability of the protein-ligand complexes in the TIP3P model. MMGBSA and MMPBSA values of 8d were ?42.46 Kcal/mol and ?14.58 Kcal/mol, respectively. Further in-vitro antitubercular screening of compounds 8a, 8d, and 8e against M. tuberculosis H37Ra using XRMA protocol exhibited promising antimycobacterial activity with IC50 values 21.82μg/mL, 15.55 μg/mL, and 16.56 μg/mL, respectively. Compounds 8a, 8d, and 8e showed antibacterial activity with IC50 values 41.56 μg/mL, 24.72 μg/mL, and 72.45 μg/mL respectively against the Staphylococcus aureus. 8a and 8d showed inhibition with IC50 values 39.6 μg/mL and 27.64 μg/mL, respectively, against Bacillus subtilis. The present study could help in the further development of lead molecules against tuberculosis.
- Puranik, Ninad V.,Swami, Sagar,Misar, Ashwini V.,Mamgain, Ritu,Gulawani, Swapnaja S.,Sarkar, Dhiman,Srivastava, Pratibha,Srivastava, Pratibha
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supporting information
(2021/03/15)
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- Identification of novel androgen receptor degrading agents to treat advanced prostate cancer
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Prostate cancer (PCa) is one of the most common malignancies affecting men worldwide. Androgen receptor (AR) has been a target of PCa treatment for nearly six decades. AR antagonists/degraders can effectively treat PCa caused by increased AR overexpression. However, all approved AR antagonists have similar chemical structures and exhibit the same mode of action on the protein. Although initially effective, resistance to these AR antagonists usually develops. Therefore, this calls for the identification of novel chemical structures of AR antagonists to overcome the resistance. Herein, we employed the synergetic combination of virtual and experimental screening to identify a flavonoid compound which not only effectively inhibits AR transcriptional activity, but also induces the degradation of the protein. Based on this compound, we designed and synthesized a series of derivatives. We discovered that the most potent compound 10e could effectively inhibit AR transcriptional activity, and possessed a profound ability to cause degradation of both full length- and ARv7 truncated forms of human AR. Notably, 10e efficiently inhibited the growth of ARv7 dependent prostate cancer cell-lines, which are completely resistant to all current anti-androgens. Compound 10e also showed strong antitumor activity in the LNCaP (androgen dependent prostate cancer cell line) in vivo xenograft model. These results provide a foundation for the development of a new class of AR antagonists.
- Wu, Hongxi,Ren, Jie,Zhao, Lulu,Li, Zhiyu,Ye, Wanli,Yang, Yong,Wang, Jubo,Bian, Jinlei
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- Anti‐melanogenic properties of velutin and its analogs?
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Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti‐inflammatory, anti‐allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti‐melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2‐diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural‐derived functional materials to regulate melanin synthesis.
- Choe, Jung-Won,Heo, Hee-Young,Jung, Se-Hui,Kim, Jaehyun,Lee, Kooyeon
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- Application of human PCID2 protein in preparation or screening of anti-tumor drugs and compound with anti-tumor activity
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The invention belongs to the technical field of biotechnology and gene therapy, and particularly relates to application of human PCID2 protein in preparation or screening of anti-tumor drugs and an anti-tumor compound. It is found that the PCID2 gene promotes tumor cell proliferation and regulates the cell cycle, is a key molecule for regulating tumor generation and development, and can be used as a target protein for preparing or screening anti-tumor drugs; meanwhile, human PCID2 protein is used as target protein, a class of PCID2 protein targeting antitumor compounds are screened out through a molecular docking technology, and the compounds can significantly inhibit tumor cell proliferation and promote tumor cell apoptosis.
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Paragraph 0094-0096
(2021/06/02)
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- SYNTHESIS OF MORIN AND MORIN DERIVATIVES
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The invention relates to a method for directly producing morin derivatives and high-purity morin of formula (I). The invention also relates to morin derivatives and high-purity morin that can be obtained using the claimed method.
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Paragraph 0034
(2020/11/24)
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- Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors
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The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC50 of 72 ± 2 nM and its 8-C-glucoside orientin with an IC50 of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 ? resolution and quambalarine B at 2.5 ? resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.
- Albi?ana, Carlos Berenguer,Brynda, Ji?í,Fanfrlík, Jind?ich,Flieger, Miroslav,Hodek, Jan,Karlukova, Elena,Ko?í?ek, Milan,Konvalinka, Jan,Machara, Ale?,Majer, Pavel,Radilová, Kate?ina,Weber, Jan,Zima, Václav
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supporting information
(2020/09/09)
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- Synthesis method of isolicoflavonol
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The invention provides a synthesis method of isolicoflavonol, which comprises the following steps: carrying out condensation reaction on 2,4-O-R1(protective group, the same below)-6-hydroxyacetophenone and 4-O-R2(protective group, the same below)-benzaldehyde to generate 2',4'-O-R1-6'-hydroxy-4-O-R2-chalcone; oxidizing the chalcone to generate flavonol; carrying out selective protection on 3-OH ofthe flavonol to obtain 3,5,7-O-R1-4'-O-R2-flavonol; removing the protecting group R2 from the 3,5,7-O-R1-4'-O-R2-flavonol to obtain 3,5,7-O-R1-4'-hydroxyflavonol; carrying out 1,1-dimethylpropargyl reaction on the 4,4'-OH site to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonol; carrying out partial hydrogenation on the alkynyl of the 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonolunder the action of a catalyst to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol and carrying out Claisen rearrangement on the 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol to obtain 3,5,7-O-R1-isolicoflavonol, and removing the protecting group R1 from the 3,5,7-O-R1-isolicoflavonol to obtain the isolicoflavonol.
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Paragraph 0111; 0149-0154
(2020/12/29)
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- Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation
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Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 μM (IC50 = 6.4 μM) with the lowest cytotoxicity (IC50 > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.
- Chen, Lijuan,Fan, Tiantian,Lei, Xiangui,Teichmann, Alexander Tobias,Wang, Amu,Wang, Chao,Wei, Zhe,Wieland, Frank Heinrich,Yang, Youzhe,Yin, Jinxiang,Zhou, Li,Zhu, Yue
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supporting information
(2020/03/24)
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- Design, synthesis and biological evaluation of dimethyl cardamonin (DMC) derivatives as P-glycoprotein-mediated multidrug resistance reversal agents
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Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting P-gp to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp. Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism design on the basis of Dimethyl Cardamonin (DMC). Subsequently, we evaluated their reversal activities as potential P-glycoprotein (P-gp)-mediated Multidrug Resistance (MDR) agents. Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the corresponding benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. Their cytotoxicity and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 was evaluated by Doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply. Results and Discussion: The results showed that compounds B2, B4 and B6 had the potency of MDR reversers with little intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the capability to inhibit MCF-7 and MCF-7/DOX cells migration. Besides, the most compound B4 was selected for further study, which promoted the accumulation of DOX in MCF-7/DOX cells and inhibited the expressionof P-gp at protein levels. Conclusion: The above findings may provide new insights for the research and development of P-gp-mediated MDR reversal agents.
- Liu, Jianwen,Ma, Lei,Shi, Ximeng,Yin, Huanhuan,Zhao, Yuyu,Zhou, Licheng
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p. 1270 - 1282
(2020/10/06)
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- Design and synthesis of novel Flavone-based histone deacetylase inhibitors antagonizing activation of STAT3 in breast cancer
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Histone deacetylases (HDACs) inhibitors have demonstrated a great clinical achievement in hematological malignancies. However, the efficacy of HDACs inhibitors in treating solid tumors remains limited due to the complicated tumor microenvironment. In this study, we designed and synthesized a class of novel HDACs inhibitors based on the structure of flavones and isoflavones, followed by biological evaluation. To be specific, a lead compound 15a was discovered with strong anti-proliferative effects on a variety of solid tumor cells, especially for breast cancer cells with resistance to SAHA. Studies demonstrated that 15a could significantly inhibit the activity of HDAC 1, 2, 3 (class I) and 6 (class IIB), leading to a dose-dependent accumulation of acetylated histones and α-Tubulin, cell cycle arrest (G1/S phase) and apoptosis in breast cancer cells. Furthermore, the lead compound 15a could also antagonize the activation of STAT3 induced by HDACs inhibition in some breast cancer cells, which further reduced the level of pro-survive proteins in tumor cells and enhanced anti-tumor activity regulated by STAT3 signaling in vivo. Overall, our findings demonstrated that the novel compound 15a might be a HDACs inhibitor candidate, which could be used as promising chemotherapeutic agent for breast cancer.
- Wei, Mingming,Xie, Maodun,Zhang, Zhen,Wei, Yujiao,Zhang, Juan,Pan, Hongli,Li, Benlong,Wang, Jingjing,Song, Yang,Chong, Chuangke,Zhao, Rui,Wang, Jiefu,Yu, Li,Yang, Guang,Yang, Cheng
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- Synthetic method for portulacanone compounds and their derivatives and anti-inflammatory pharmaceutical compounds containing thereof
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The present inventors synthesized described portulacanone derivatives (compound 1: R^1, R^2 = H; and compound 2: R^1, R^2 = H), natural homoisoflavonoids (andplusmn;)-portulacanone A-C (compound 4: R^1 = OMe, R^2 = H; compound 8: R^1, R^2 = OMe; and compound 9: R^1 = OH, R^2 = OMe), and derivatives thereof (compound 3: R^1 = OMe, R^2 = H; compound 5: R^1 = OH, R^2 = H, and compound 7: R^1, R^2 = OMe), and thus evaluated ability to inhibit NO production in LPS-induced RAW 264.7 macrophages as an indicator of anti-inflammatory activity. All tested compounds showed no clear cytotoxicity and inhibited NO production in a concentration dependent manner in RAW 264.7 macrophages. A compound 3 (97.2% inhibition at 10 andmu;M; IC50 = 1.26 andmu;M) shows a significant inhibition effect compared to a compound 1 (91.4% inhibition at 10 andmu;M; IC50 = 1.75 andmu;M) and a compound 7 (83.0% inhibition at 10 andmu;M; IC50 = 2.91 andmu;M). Compounds of the present invention are useful for developing NO producing targeted anti-inflammatory drugs.COPYRIGHT KIPO 2019
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- Synthetic method for portulacanone D and anti-inflammatory pharmaceutical compounds containing thereof
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Inventors of the present invention synthesized natural homoisoflavonoid portulacanone D (compound 6) isolated from Portulaca oleracea L (POL). An ability to inhibit NO production in LPS-induced RAW 264.7 macrophages was assessed as an indicator of anti-inflammatory activity. The tested portulacanone D did not show clear cytotoxicity and inhibited NO production in the RAW 264.7 macrophages in a concentration dependent manner. The portulacanone D exhibits 92.5% of NO production inhibition at 10 andmu;M and has an IC50 value of 2.09 andmu;M. The finding has additional correlation with the suppressed expression of iNOS induced by LPS. According to the information obtained from the study of the present invention, the portulacanone D can be used in the development of anti-inflammatory drugs targeting NO production.COPYRIGHT KIPO 2019
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- Chemical Synthesis Enables Structural Reengineering of Aglaroxin C Leading to Inhibition Bias for Hepatitis C Viral Infection
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As a unique rocaglate (flavagline) natural product, aglaroxin C displays intriguing biological activity by inhibiting hepatitis C viral entry. To further elucidate structure-activity relationships and diversify the pyrimidinone scaffold, we report a concise synthesis of aglaroxin C utilizing a highly regioselective pyrimidinone condensation. We have prepared more than 40 aglaroxin C analogues utilizing various amidine condensation partners. Through biological evaluation of analogues, we have discovered two lead compounds, CMLD012043 and CMLD012044, which show preferential bias for the inhibition of hepatitis C viral entry vs translation inhibition. Overall, the study demonstrates the power of chemical synthesis to produce natural product variants with both target inhibition bias and improved therapeutic indexes.
- Zhang, Wenhan,Liu, Shufeng,Maiga, Rayelle I.,Pelletier, Jerry,Brown, Lauren E.,Wang, Tony T.,Porco, John A.
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supporting information
p. 1312 - 1323
(2019/01/21)
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- Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors
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Rocaglates are a family of natural products isolated from the genus Aglaia which possess a highly substituted cyclopenta[b]benzofuran skeleton and inhibit cap-dependent protein synthesis. Rocaglates are attractive compounds due to their potential for inhibiting tumor cell maintenance in vivo by specifically targeting eukaryotic initiation factor 4A (eIF4A) and interfering with recruitment of ribosomes to mRNA. In this paper, we describe an intercepted retro-Nazarov reaction utilizing intramolecular tosyl migration to generate a reactive oxyallyl cation on the rocaglate skeleton. Trapping of the oxyallyl cation with a diverse range of nucleophiles has been used to generate over 50 novel amidino-rocaglate (ADR) and amino-rocaglate derivatives. Subsequently, these derivatives were evaluated for their ability to inhibit cap-dependent protein synthesis where they were found to outperform previous lead compounds including the rocaglate hydroxamate CR-1-31-B.
- Zhang, Wenhan,Chu, Jennifer,Cyr, Andrew M.,Yueh, Han,Brown, Lauren E.,Wang, Tony T.,Pelletier, Jerry,Porco, John A.
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supporting information
p. 12891 - 12900
(2019/09/09)
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- Evaluation of the inhibitory effects of (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (DiNap), a natural product Analog, on the replication of type 2 PRRSV in vitro and in vivo
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DiNap [(E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one], an analog of a natural product (the chalcone flavokawain), was synthesized and characterized in this study. Porcine reproductive and respiratory syndrome virus (PRRSV) is the most challenging threat to the swine industry worldwide. Currently, commercially available vaccines are ineffective for controlling porcine reproductive and respiratory syndrome (PRRS) in pigs. Therefore, a pharmacological intervention may represent an alternative control measure for PRRSV infection. Hence, the present study evaluated the effects of DiNap on the replication of VR2332 (a prototype strain of type 2 PRRSV). Initially, in vitro antiviral assays against VR2332 were performed in MARC-145 cells and porcine alveolar macrophages (PAMs). Following this, a pilot study was conducted in a pig model to demonstrate the effects of DiNap following VR2332 infection. DiNap inhibited VR2332 replication in both cell lines in a dose-dependent manner, and viral growth was completely suppressed at concentrations ≥0.06 mM, without significant cytotoxicity. Consistent with these findings, in the pig study, DiNap also reduced viral loads in the serum and lungs and enhanced the weight gain of pigs following VR2332 infection, as indicated by comparison of the DiNap-treated groups to the untreated control (NC) group. In addition, DiNap-treated pigs had fewer gross and microscopic lesions in their lungs than NC pigs. Notably, virus transmission was also delayed by approximately 1 week in uninfected contact pigs within the same group after treatment with DiNap. Taken together, these results suggest that DiNap has potential anti-PRRSV activity and could be useful as a prophylactic or post-exposure treatment drug to control PRRSV infection in pigs.
- Khatun, Amina,Park, Sun You,Shabir, Nadeem,Nazki, Salik,Kang, A-Rum,Jeong, Chang-Gi,Seo, Byoung-Joo,Yang, Myeon-Sik,Kim, Bumseok,Seo, Young Ho,Kim, Won-Il
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- Synthesis of flavone derivatives via N-amination and evaluation of their anticancer activities
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Seventeen new flavone derivatives substituted at the 40-OH position were designed, synthesized and evaluated for their anticancer and antibacterial activities. Among them, compounds 3, 4, 6f, 6e, 6b, 6c and 6k demonstrated the most potent antiproliferative activities against a human erythroleukemia cell line (HEL) and a prostate cancer cell line (PC3). The results also showed that the IC50 value of compounds 3, 4, 6f, 6e, 6b, 6c and 6k were close to that of the anticancer drug cisplatin (DDP) and lower than that of apigenin. All of the derivatives did not present antibacterial activities. The structure–activity relationships evaluation showed that the configuration of methyl amino acid might affect their biological activities.
- Zhang, Ni,Yang, Jin,Li, Ke,Luo, Jun,Yang, Su,Song, Jun-Rong,Chen, Chao,Pan, Wei-Dong
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- Flavonoid derivative with tumor cell inhibition and preparation method and application thereof
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The invention relates to a flavonoid derivative and a preparation method and application thereof. A coupling reaction is used to prepare the flavonoid derivative, 4'-OH is replaced with an amino substituted substance, and a nitrogen-containing derivative is synthesized on a flavonoid skeleton. By introducing the amino substituted substance, hydrogen bonding of the flavonoid derivative and a target protein can be regulated, and at the same time, an ester water partition coefficient can be also regulated, so that the flavonoid derivative can pass a blood-brain barrier relatively well, and thereby plays a role in inhibiting tumor cells. An anti-proliferative activity research of the flavonoid derivative in tumor cells HEL and PC3 is studied by MTT assay, results show that the flavonoid derivative has good anti-proliferative activity against the tumor cells HEL and PC3, and has higher antitumor activity than natural flavonoid apigenin, and the anti-proliferative effect of the flavonoid derivative is similar to that of clinical anti-tumor drug cisplatin.
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Paragraph 0016-0017
(2019/10/01)
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- Preparation method and application of tricetin
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The invention belongs to the field of medicine synthesis, and in particular relates to a preparation method and application of tricetin. The method comprises the following steps: performing hydroxy protection to form a compound 3 by using 2,4,6-trihydroxyacetophenone as a starting material, performing an acylation reaction on the compound 3 and 3,4,5-trimethoxybenzoyl chloride to form a compound 4, performing Baker-Venkataranan rearrangement on the compound 4 to form a compound 5, performing cyclization on the compound 5 under catalysis of H2SO4/HOAc to form a compound 6, and finally performing pyridine hydrochloride deprotection on the compound 6 to form the tricetin, wherein in the step of synthesizing the compound 5, when NaOH is selected as a base and pyridine is selected as a solvent,the yield is greatly improved, and the reaction is relatively stable. According to the method provided by the invention, pharmacological activity experiments show that the compound synthesized by themethod has anti-nerve damage activity, so that the compound has better application prospects in treating nerve damage-related diseases.
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Paragraph 0007; 0063-0065
(2019/10/01)
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- The winding road of the uvaretin class of natural products: From total synthesis to bioactive agent discovery
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Herein, we disclose the development of a synthetic route to gain access to the uvaretin class of chalcone natural products. In this, the construction of a small library was achieved, and the collection was evaluated for cytotoxicity and other biological properties. Uvaretin (1) was accessed via a seven-step route in an overall yield of 15.1%. Within this route, the unsaturated enone variant of uvaretin (2), also a natural product, was accessed in a 16.7% yield over six steps. This route provides a nearly three-fold increase in yields of 1 and 2 in comparison to the previous synthetic route accessing them in 5.8% and 3.0% overall yields, respectively. Evaluation of 1 and 2 revealed IC50 values between 2.0 and 5.1 μM in the cancerous cell lines HeLa, U937, A549, and MIA PaCa-2. Screening of the whole chalcone library set led to the discovery of over 30 compounds, within six cancerous cell lines, possessing single digit μM IC50 activity as sole agents. Furthermore, multiple library members were found to possess promising potentiating properties with known chemotherapeutic agents.
- Dallman, Johnathan,Lansakara, Ashabha,Nguyen, Thi,Weeramange, Chamitha,Hulangamuwa, Wasundara,Rafferty, Ryan J.
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p. 1420 - 1431
(2019/08/21)
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- Method for preparing dewatered icaritin through total-synthesis
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The invention provides a method for preparing dewatered icaritin through total-synthesis. The method includes the steps of connecting an isopentene group to 8th-position carbon through ortho-positionrearrangement with methoxybenzoyl chloride, isoprenyl bromide and the like as the raw materials by means of trihydroxyacetophenone, and conducting the forming series reaction of a flavone framework toobtain the dewatered icaritin. The defects that in a traditional method of introducing an isopentene group, the yield is low, catalysts are expensive and lots of byproducts are produced are overcome,and the method is low in cost, simple in operation, good in yield and suitable for industrial production.
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Page/Page column 9; 11; 13; 17
(2019/06/07)
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- Design of wogonin-inspired selective cyclin-dependent kinase 9 (CDK9) inhibitors with potent in vitro and in vivo antitumor activity
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Wogonin, a natural product isolated from the plant Scutellaria baicalensis, has been shown to be a potent and selective inhibitor of CDK9. With the purpose of investigating the activity and selectivity of this chemical scaffold, several series of wogonin derivatives were prepared and screened for CDK9 inhibition and cellular antiproliferative activity. Among these compounds, the drug-like compound 51 showed potent activity against CDK9 (IC50 = 19.9 nM) and MV4-11 cell growth (IC50 = 20 nM). In addition, compound 51 showed much improved physicochemical properties, such as water solubility, compared with the parent compound wogonin. The follow-up studies showed that the compound 51 is selective toward CDK9-overexpressing cancer cells over normal cells. Preliminary mechanism studies on the anticancer effect indicated that 51 inhibited the proliferation of MV4-11 cells via caspase-dependent apoptosis. In addition, highlighted compound 51 showed significant antitumor activity in mouse acute myeloid leukemia (AML) models without producing apparent toxic effects in vivo, which gave us a new tool for further investigation of CDK9-targeted inhibitor as a potential antitumor drug especially for AML.
- Wang, Jubo,Li, Tinghan,Zhao, Tengteng,Wu, Tizhi,Liu, Chuang,Ding, Hong,Li, Zhiyu,Bian, Jinlei
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p. 782 - 801
(2019/06/25)
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- Novel CDK9 inhibitor based on benzofuran structure, preparation method and application of novel CDK9 inhibitor
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The invention relates to the field of biological medicine, in particular to a series of derivatives of a novel CDK9 inhibitor with a benzofuran structure and an application of the novel CDK9 inhibitor. A series of compounds are synthesized by modifying a parent nucleus of wogonin since wogonin has the disadvantages of low antitumor activity and poor druggability; particularly, an N-ring containingsubstituent is introduced into a 3' site or a 4' site; the compounds are brand-new and are not reported in literatures; at the same time, the inventor carries out a series of bioactivity evaluation on the synthesized compounds; and in particular, the most compounds have good selectivity for CDK9 and better inhibition activity for cancer cells.
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Paragraph 0039; 0040; 0043; 0044
(2019/08/01)
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- Compound for treating or preventing hepatopathy (by machine translation)
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The invention discloses a compound, an optical isomer or a pharmaceutically acceptable salt, an optical isomer or a pharmaceutically acceptable salt thereof for treating or preventing hepatopathy, and the compound, optical isomer or pharmaceutically acceptable salt thereof can be applied to the preparation of a medicine for treating or preventing liver diseases. (by machine translation)
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Paragraph 0211-0212; 0213
(2019/10/01)
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- AGENTS AND METHODS FOR TREATING DYSPROLIFERATIVE DISEASES
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Compounds are described with the general formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, and n are defined as anywhere herein, which are useful for the treatment of cancer and other dysproliferative diseases.
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Paragraph 00132-00133
(2019/09/04)
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- Total synthesis of wikstrol A and wikstrol B
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The first total synthesis of wikstrol A and wikstrol B was achieved by employing aldol reaction, Sharpless asymmetric dihydroxylation, regioselective iodination, Sonogashira coupling, and rhodium-catalyzed oxidative coupling as key steps. The structure of the key intermediate for wikstrol A was confirmed via its derivative by single-crystal X-ray analysis.
- Lu, Kui,Li, Ming,Huang, Yuna,Sun, Yuanyuan,Gong, Zhi,Wei, Qijun,Zhao, Xia,Zhang, Yongmin,Yu, Peng
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p. 8206 - 8213
(2019/09/19)
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- 3-site piperazinylchalcone derivative, and pharmaceutical composition and applications thereof
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The present invention relates to a 3-site piperazinylchalcone derivative, which has a structure formula represented by a general formula (I) defined in the specification, wherein R is one selected from a substituted or unsubstituted phenyl group, a fused ring group and substituted or a unsubstituted heterocyclic group. The present invention further provides a pharmaceutical composition of the3-site piperazinylchalcone derivative, and applications thereof. According to the present invention, the results of the activity test based on P-gp target show that the 3-site piperazinylchalcone derivative and the pharmaceutical composition have good activity, can provide practical value in the treatment of the multidrug resistance of tumors, can solve the technical problems of difficult synthesis and high cost in the synthesis of the reversing agent used in the prior art, and is meaningful.
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Paragraph 0070-0074; 0084-0086; 0093; 0094
(2019/02/04)
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- Design, synthesis and biological evaluation of chalcones as reversers of P-glycoprotein-mediated multidrug resistance
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Overexpression of P-glycoprotein (P-gp) is one of the major causes for multidrug resistance (MDR), which has become a major obstacle in cancer therapy. One hopeful approach to reverse the MDR is to develop inhibitors of P-gp in expression and/or function. Here, we designed and synthesized a series of chalcone derivatives as P-gp inhibitors and evaluated their potential reversal activities against MDR. Among them, the most active compound MY3 had little intrinsic cytotoxicity and showed the highest activity (RF = 50.19) in reversing DOX resistance in MCF-7/DOX cells. Further studies demonstrated that MY3 could increase intracellular accumulation of DOX and inhibit expression of P-gp at mRNA and protein levels. More importantly, MY3 significantly enhanced the efficacy of DOX against the tumor xenografts bearing MCF-7/DOX cells with the precondition of unchanged body weight. Therefore, MY3 might represent a promising lead to develop MDR reversal agents for cancer chemotherapy.
- Yin, Huanhuan,Dong, Jingjing,Cai, Yingchun,Shi, Ximeng,Wang, Hao,Liu, Guixia,Tang, Yun,Liu, Jianwen,Ma, Lei
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p. 350 - 366
(2019/07/19)
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- Synthesis and in vitro evaluation of homoisoflavonoids as potent inhibitors of nitric oxide production in RAW-264.7 cells
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Syntheses of natural homoisoflavonoids, (±)-portulacanones A–C (4, 8 and 9), portulacanone D (6), isolated from Portulaca oleracea L. (POL) and their derivatives (3, 5 and 7) have been achieved for the first time along with the synthesis of known derivatives (1 and 2) and their in vitro inhibitory effect against NO production in LPS-induced RAW-264.7 macrophages was evaluated as an indicator of anti-inflammatory activity. All the compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without obvious cytotoxicity. Compounds 3 (97.2% at 10 μM; IC50 = 1.26 μM) followed by 6 (portulacanone D) (92.5% at 10 μM; IC50 = 2.09 μM), 1 (91.4% at 10 μM; IC50 = 1.75 μM) and 7 (83.0% at 10 μM; IC50 = 2.91 μM) were the most potent from the series. This finding was further correlated with the suppressed expression of iNOS induced by LPS. Our promising preliminary results may provide the basis for the assessment of compound 3 as a lead structure for a NO production-targeted anti-inflammatory drug development and also could support the usefulness of POL as a folklore medicinal plant in the treatment of inflammatory diseases.
- Damodar, Kongara,Lee, Jeong Tae,Kim, Jin-Kyung,Jun, Jong-Gab
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p. 2098 - 2102
(2018/04/30)
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- Flavone derivative and application thereof
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The invention discloses a flavone derivative and the application thereof. The flavone derivative is a compound with multiple target points and multiple functions for preventing Alzheimer's diseases. The compound and a pharmaceutical salt thereof can be applied to preparation of corresponding medicines, and the compound can be also applied to antioxidants, multiple enzyme inhibitors and metal chelating agents.
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Paragraph 0033-0035; 0038-0039
(2021/02/24)
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- Design and synthesis of novel 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives as potent Mnks inhibitors by fragment-based drug design
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A novel series of 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide derivatives featured with various C-2 substituents were designed and synthesized as Mnks inhibitors through fragment-based drug design. Among them, 5b, 5i, 5o and 8k showed the best Mnk2 inhibitory activity with IC50 values of 1.45, 1.16, 3.55 and 0.27 μM, respectively. And these compounds inhibited the activity of Mnk1 at the same time. Furthermore, compounds 5o and 8k exhibited anti-proliferative effects to human leukemia cancer THP-1 and MOLM-13 cell lines and colon cancer HCT-116 cell line. Moreover, Western blot assay suggested that 8k could decrease the levels of p-eIF4E in a dose-dependent manner in HCT-116 cells. Docking studies demonstrated strong interactions between 8k and Mnk2. Therefore, this unique benzofuran scaffold demonstrated great potential to be further explored as potent Mnks inhibitors with improved potency.
- Wang, Shuxiang,Li, Bo,Liu, Bo,Huang, Min,Li, Deyi,Guan, Lihong,Zang, Jie,Liu, Dan,Zhao, Linxiang
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p. 4602 - 4614
(2018/08/20)
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- Synthesis of Benzopyran-Fused Flavone Derivatives via Microwave-Assisted Intramolecular C-H Activation
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A microwave-assisted intramolecular direct arylation method for the synthesis of benzopyran-fused flavone derivatives containing natural flavone backbones is described. Different polyalkoxy flavones were synthesized and functionalized with 2-bromobenzyl bromide. The resulting compounds were subjected to palladium-catalyzed intramolecular direct arylation reactions supported by microwave irradiation to produce fused tetracyclic flavones. In the case of the 7-substituted chrysin derivative, the regioselectivity of the coupling was also examined.
- Sipos, Zoltán,Kónya, Krisztina
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supporting information
p. 1610 - 1620
(2018/03/21)
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- Synthesis and antiproliferative activity of aminoalkylated chalcones on three human cancer cells
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Abstract: Two series of 16 novel aminoalkylated chalcone derivatives 2a–h and 3a–h were synthesized from 2′-hydroxy-3,4,4′,6′-tetramethoxychalcone (1) through extending alkoxy side chain at the 2′-position, and introducting amine hydrogen bond receptor at the end of the side chain. Their in vitro antiproliferative activities were evaluated on a panel of three human cell lines (Hela, HCC1954, and SK-OV-3) by CCK-8 assay. The results showed that all the target compounds, except compound 3e, exhibited moderate to potent antiproliferative activities against these three human cancer cells with the IC50 values of 6.78–64.45 μmol/L, in particular compounds 2g (on Hela cells), 2c (on HCC1954 cells), and 2c, 2d (on SK-OV-3 cells) possess IC50 values below 10 μmol/L. It showed the introduction of aminoalkyl moiety at 2′-O-position of chalcone 1 resulted to produce the desired effect of increasing the antiproliferative activities, and the distance between the amino groups and chalcone moiety plays an important role, the optimal number of methylene units is two-carbon spacer. Graphical abstract: A series of 16 novel aminoalkylated chalcones were synthesized and their antiproliferative acivities on three human cancer cells were evaluated. [InlineMediaObject not available: see fulltext.].
- Li, Cui,Wang, Gangqiang,Li, Xueli,Wang, Qiuan
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p. 972 - 979
(2017/11/29)
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- Design and synthesis of aminoester heterodimers containing flavone or chromone moieties as modulators of P-glycoprotein-based multidrug resistance (MDR)
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In this study, a new series of heterodimers was synthesized. These derivatives are N,N-bis(alkanol)amine aryl esters or N,N-bis(ethoxyethanol)amine aryl esters carrying a methoxylated aryl residue combined with a flavone or chromone moiety. The new compounds were studied to evaluate their P-gp modulating activity on a multidrug-resistant leukemia cell line. Some of the new compounds show a good MDR reversing activity; interestingly this new series of compounds does not comply with the structure-activity relationships (SAR) outlined by previously synthesized analogs carrying different aromatic moieties. In the case of the compounds described in this paper, activity is linked to different features, in particular the characteristics of the spacer, which seem to be critical for the interaction with the pump. This fact indicates that the presence of a flavone or chromone residue influences the SAR of these series of products, and that flexible molecules can find different productive binding modes with the P-gp recognition site. These results support the synthesis of new compounds that might be useful leads for the development of drugs to control P-gp-dependent MDR.
- Dei, Silvia,Romanelli, Maria Novella,Manetti, Dina,Chiaramonte, Niccolò,Coronnello, Marcella,Salerno, Milena,Teodori, Elisabetta
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- Unveiling the 6,8-Rearrangement in 8-Phenyl-5,7-dihydroxyflavylium and 8-Methyl-5,7-dihydroxyflavylium through Host–Guest Complexation
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8-Phenyl-5,7-dihydroxyflavylium and 8-methyl-5,7-dihydroxyflavylium were synthesized to observe the 6,8-rearrangement. 8-Phenyl and 8-methyl residues were introduced by Suzuki–Miyaura reaction of 8-iodochrysin, then reduced by LiAlH4 to give the corresponding 3-deoxyanthocyanidins. At pH 1.0 the stable form is the 8-substituted flavylium cation in both compounds. At higher pH values the quinoidal bases are the stable species and some evidence for the 6,8-rearrangement was obtained, but the respective spectral variations are very small. This was overcome by using a modified cyclodextrin (captisol), which favors the formation of the trans-chalcone at the expense of the quinoidal bases. The trans-chalcone was isolated and dissolved in CD3OD/DCl (pD + m/z 253). The 6-isomer slowly reverts to the most stable 8-isomer. The 6,8-rearrangement was also observed after irradiation of the trans-chalcone (in the presence of captisol) at pH 5. Acidification of this photostationary state gave a mixture of both flavylium cations. The UV/Vis absorption of the flavylium cation (6-isomer) was blueshifted in comparison to the 8-isomer.
- Basílio, Nuno,Lima, Jo?o Carlos,Cruz, Luís,de Freitas, Victor,Pina, Fernando,Ando, Hiroki,Kimura, Yuki,Oyama, Kin-Ichi,Yoshida, Kumi
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supporting information
p. 5617 - 5626
(2017/10/13)
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- New homoisoflavonoid analogues protect cells by regulating autophagy
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As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide. Six cardioprotective compounds with representative structure diversities were then evaluated for their neuroprotective effects on MPP+ induced SH-SY5Y cell injury model. Furthermore, autophagy inducing monodansylcadaverine (MDC) fluorescence staining methods and molecular docking studies indicated the action mechanism of these compounds may involve autophagy regulating via class I PI3K signaling pathway.
- Gan, Li-She,Zeng, Lin-Wei,Li, Xiang-Rong,Zhou, Chang-Xin,Li, Jie
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supporting information
p. 1441 - 1445
(2017/03/08)
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- With apigenin skeleton derivative and its preparation and use
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The invention discloses a derivative having an apigenin framework, a preparation method and an application thereof. The derivative is a compound represented as the general formula (I) or pharmaceutically acceptable salt thereof, wherein R is represented as one in the following two structures. The derivative has excellent activity of resisting cervical cancer and liver cancer, is multiple in target point, has multiple links and multiple response, is low in toxicity and is not liable to cause drug resistance.
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Paragraph 0036; 0037; 0047; 0048; 0054; 0058; 0059; 0069
(2018/11/04)
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- 3,5-DISUBSTITUTED PYRAZOLES USEFUL AS CHECKPOINT KINASE 1 (CHK1) INHIBITORS, AND THEIR PREPARATIONS AND APPLICATIONS
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Potent inhibitors of Chk1 have the structure formula (I) below. Pharmaceutical compositions comprising the Chk1 inhibitors, uses thereof and their preparation process.
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- The total synthesis of (±)-sanggenol F
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A concise and efficient total synthesis of sanggenol F (1) in racemic form has been completed via a sequence of 15 steps with an overall yield of 3.1%, starting from commercially available 2,4,6-trihydroxyacetophenone. Meanwhile, a semisynthesis of sanggenol F racemate has also been achieved in 11.1% overall yield via 7 steps with naturally-occurring morin (2) as the starting material. One step and a stepwise approach were employed to construct the two prenyl side chains at 2- and 6-positions by Claisen rearrangement reaction.
- Sheng, Xiao,Jia, Xin-Yu,Tang, Fei,Wang, Yang,Hou, Ai-Jun
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p. 3485 - 3491
(2017/06/01)
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- Total synthesis of agalloside, isolated from: Aquilaria agallocha, by the 5-O-glycosylation of flavan
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Agalloside (1) is a neural stem cell differentiation activator isolated from Aquilaria agallocha by our group using Hes1 immobilized beads. We conducted the first total synthesis of agalloside (1) via the 5-O-glycosylation of flavan 25 using glycosyl fluoride 20 in the presence of BF3·Et2O. Subsequent oxidation with DDQ to flavanone 2 and deprotection successively provided agalloside (1). This synthetic strategy holds promise for use in the synthesis of 5-O-glycosylated flavonoids. The synthesized agalloside (1) accelerated neural stem cell differentiation, which is a result comparable to that for the naturally occurring compound 1.
- Arai, Midori A.,Yamaguchi, Yumi,Ishibashi, Masami
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p. 5025 - 5032
(2017/07/10)
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- Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity
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The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50lower than 10?μM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities.
- Yang, Chao,Chen, Hui,Lu, Shihai,Zhang, Meng,Tian, Wei,Wang, Mingping,Zhang, Ling,Song, Yunlong,Shen, Aijun,Zhou, Youjun,Zhu, Ju,Zheng, Canhui
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p. 3464 - 3467
(2016/07/21)
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- Formal total synthesis of artocarpin
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A formal total synthesis of artocarpin was achieved via selective demethylation, iodination, followed by Suzuki-Miyaura coupling reaction of the key flavone derivative. It took only 7 steps in the overall yield of 55% starting from commercially available 3,5-dimethoxyphenol.
- Mizota, Isao,Taniguchi, Kana,Shimizu, Makoto
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p. 310 - 322
(2017/03/14)
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- An improved synthesis of apigenin and luteolin
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Apigenin and luteolin are the antioxidant flavonoids found in foods such as parsley, artichoke, basil and celery. Both of these compounds have shown the ability to protect cells against cancer and also to inhibit DNA oxidative damage. These flavonoids are part of many nutraceutical formulations available in the market. There is a need for the development of cost effective methodologies to produce them in large quantities. The synthetic process developed for both these compounds is general and can be applied for other flavonoids also. An industrially applicable high pure product, cost effective synthesis and general synthetic method has been developed and presented.
- Rambabu,Kumari,Baby Ramana,Ramani,Subbaraju,Hari Babu
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p. 1139 - 1143
(2016/03/01)
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- Natural product Hirtellanine B and its derivatives in the preparation process for the preparation of medicine for treating tumor with the application of the
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The present invention provides a preparation method of a natural product Hirtellanine B, wherein 2,4,6-trihydroxyacetophenone is adopted as a raw material, and steps of compound a preparation, compound b preparation, compound c preparation, compound d preparation, compound e preparation, compound f preparation, compound g preparation, and the like are performed to prepare the natural product Hirtellanine B. According to the present invention, biological activity screening is performed on Hirtellanine B and 14 Hirtellanine B derivatives, and results show that the natural product Hirtellanine B can inhibit proliferations of Jurkat cells, Raji cells and K562 cells, and the compounds provide a certain inhibition activity for tumor cells. The method has characteristics of easily available raw material, high reaction yield and reasonable operation, and is suitable for industrial production. The Hirtellanine B and the derivatives thereof can be used for preparing tumor treatment drugs, and have great clinical values. The natural product Hirtellanine B preparation method reaction formulas are as the follows.
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Paragraph 0056; 0144
(2016/10/10)
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- 4 - aromatic amine - coumarin derivatives and its preparation method and medical use (by machine translation)
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The invention relates to the field of pharmaceutical chemistry, in particular relates to a series of 4?Aromatic amine?Coumarin derivatives, method for their preparation and use in medicine, in particular for the treatment of tumor, such as breast cancer, and the like. The present invention relates to compounds of the general structure is as follows, each group in the formula is defined in the specification. (by machine translation)
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Paragraph 0042; 0043; 0104; 0105; 0106
(2016/11/21)
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- 5, 7, 2 ,, 4 ,-four hydroxy-3-hydrocarbyl flavone analogs and its preparation method and application (by machine translation)
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The invention discloses 5,7,2',4'-tetrahydroxy-3-alkyl flavone analog. On the basis of 5,7,2',4'-tetrahydroxy-3-geranyl (isopentene group) flavone and with the combination of the characteristics that due to the fact that alkylate medicine is extremely sensitive to malignant cells, alkylate medicine can well inhibit and eliminate activity of cancer cells, the inventor studies and prepares (+/-) 5,7,2',4'-hydroxyl (methoxyl)-3-(3,7-dimethyl octane) flavone with the flavonoid compound skeletal structure and 5,7,2',4'-hydroxyl (methoxyl)-3-(3-metryl butane) flavone with the flavonoid compound skeletal structure, conducts total synthesis on the (+/-) 5,7,2',4'-hydroxyl (methoxyl)-3-(3,7-dimethyl octane) flavone and the 5,7,2',4'-hydroxyl (methoxyl)-3-(3-metryl butane) flavone, and does in-depth study on the cervical cancer prevention effect and the hepatoma carcinoma cell activity. The in-vitro cancer cell activity inhibitory test shows that the compound can obviously inhibit cervical cancer Hela cells and liver cancer strain 7721 cells and can serve as candidate medicine for treating cervical cancer and liver cancer.
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Paragraph 0020; 0021
(2016/10/08)
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- Natural product analogues Albanin A/E and its preparation method and application
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The invention discloses a natural product Albanin A/E analogue. The inventor does research and prepares the natural product Albanin A/E analogue with the flavonoids compound framework structure on the basis of the natural product Albanin A and the natural product Albanin E, and complete synthesis and in-depth study of cervical cancer cell resistance activity are conducted on the natural product Albanin A/E analogue. The in-vitro cancer cell inhibition activity test shows that the compound has obvious effects on inhibiting cervical cancer Hela cells, and can be used for preparing candidate medicine for treating cervical cancer.
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Paragraph 0023; 0024
(2016/10/07)
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