- Synthesis of uracil–coumarin conjugates as potential inhibitors of virus replication
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A series of 1-[(bromophenoxy)alkyl]uracil–coumarin conjugates has been obtained through the preparation of starting 1-[(bromophenoxy)alkyl]uracil derivatives, followed by their treatment with 7-(ω-bromoalkoxy)-4-methyl-2H-chromen-2-ones. Two of the synthesized uracil–coumarin conjugates demonstrated a pronounced inhibitory activity against HCMV and VZV replication in vitro.
- Paramonova, Maria P.,Ozerov, Alexander A.,Chizhov, Alexander O.,Snoeck, Robert,Andrei, Graciela,Khandazhinskaya, Anastasia L.,Novikov, Mikhail S.
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- Knowledge-Based Design of Long-Chain Arylpiperazine Derivatives Targeting Multiple Serotonin Receptors as Potential Candidates for Treatment of Autism Spectrum Disorder
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Autism spectrum disorder (ASD) includes a group of neurodevelopmental disorders characterized by core symptoms such as impaired social interaction and communication, repetitive and stereotyped behaviors, and restricted interests. To date, there are no effective treatments for these core symptoms. Several studies have shown that the brain serotonin (5-HT) neurotransmission system is altered in both ASD patients and animal models of the disease. Multiple pieces of evidence suggest that targeting 5-HT receptors may treat the core symptoms of ASD and associated intellectual disabilities. In fact, stimulation of the 5-HT1A receptor reduces repetitive and restricted behaviors; blockade of the 5-HT2A receptor reduces both learning deficits and repetitive behavior, and activation of the 5-HT7 receptor improves cognitive performances and reduces repetitive behavior. On such a basis, we have designed novel arylpiperazine derivatives pursuing unprecedently reported activity profiles: dual 5-HT7/5-HT1A receptor agonist properties and mixed 5-HT7 agonist/5-HT1A agonist/5-HT2A antagonist properties. Seventeen new compounds were synthesized and tested in radioligand binding assay at the target receptors. We have identified the dual 5-HT1AR/5-HT7R agonists 8c and 29 and the mixed 5-HT1AR agonist/5-HT7R agonist/5-HT2AR antagonist 20b. These compounds are metabolically stable in vitro and have suitable central nervous system druglike properties.
- Lacivita, Enza,Niso, Mauro,Mastromarino, Margherita,Garcia Silva, Andrea,Resch, Cibell,Zeug, Andre,Loza, María I.,Castro, Marián,Ponimaskin, Evgeni,Leopoldo, Marcello
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- Photodegradable coumarin-derived amphiphilic dendrons for DNA binding: Self-assembly and phototriggered disassembly in water and air-water interface
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In this article, we demonstrate the self-assembly and photoresponive behavior of a novel coumarin-based amphiphilic dendron in both aqueous solution and air-water interface. The dendritic structure, namely C-IG1, was composed of a lipophilic cholesterol and hydrophilic poly(amido amine) (PAMAM) dendron, and the amphiphilic counterpart is interconnected by a photolabile coumarin carbonate ester, enabling the photoinduced degradation of the amphiphiles in protic solvents via SN1-like mechanism. A Nile red solubilization fluorescence assay suggests a low critical aggregation concentration for the micelle formation of C-IG1 in aqueous solutions (3.9 × 10?5 M); the Langmuir analysis further indicates that C-IG1 possesses significant compressibility in air-water interface, eventually forming homogeneous monolayers with a final molecular area (A0) of 36 ?2. Notably, the micelles and Langmuir monolayer are quite stable until photo-triggered dissociation based on the photocleavage of C-IG1 amphiphile activated by 365-nm incident light. Moreover, the transition in interfacial morphology of the Langmuir monolayer during the assembly and photodegradation processes also can be visually analyzed by incorporating Nile red probes with in situ monitoring through fluorescence microscopy. The thin film deposited on a glass substrate by the Langmuir-Blodgett technique also shows a photoresponsive behavior based on the change in the contact angles of a water droplet on the surface upon light stimulation. The binding affinity of C-IG1 and cyclic DNA determined by the fluorescence quenching analysis of the coumarin reporter suggests a ground-state macromolecular complexation process occurring through polyvalent interactions between the pseudodendrimers and biomacromolecules. The ethidium bromide displacement assay further indicates thus dendriplex formation at low nitrogen-to-phosphorous value (N/P 1) and confirms that the decomplexation accompanied by DNA release can be achieved through an active phototriggered route under spatiotemporal control.
- Ou, Jia-Yu,Shih, Yu-Chan,Wang, Bing-Yen,Chu, Chih-Chien
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- Synthesis of novel polyamine fluorescence sensors
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A highly selective and efficient method for the synthesis of novel polyamine fluorescence sensors is being offered. Remarkable increase of yields was observed, due to using potassium carbonate as proton trapper. The reaction is fast and easy-to-run in favorable conditions which accompanying by fewer side effects.
- Xi, Hai-Tao,Xiong, Min-Qiu,Wang, Lei-Lei,Hu, Quan-Zi,Sun, Xiao-Qiang
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- Design, synthesis and biological evaluation of new coumarin-dithiocarbamate hybrids as multifunctional agents for the treatment of Alzheimer's disease
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A series of new coumarin-dithiocarbamate hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's Disease (AD). The biological assays indicated that most of them showed potent inhibition and excellent selectivity towards acetylcholinesterase (AChE), and could inhibit self-induced β-amyloid (Aβ) aggregation. Especially, compound 4n presented the highest ability to inhibit AChE (IC50, 0.027 μM for hAChE) and good inhibition of Aβ aggregation (40.19% at 25 μM). Kinetic and molecular modeling studies revealed that 4n was a mixed-type inhibitor, which could interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, it also possessed specific metal-chelating ability, good BBB permeability and low toxicity on SH-SY5Y neuroblastoma cells. Moreover, compound 4n did not exhibit any acute toxicity in mice at doses up to 1000 mg/kg, and could reverse the cognitive dysfunction of scopolamine-induced AD mice. As far as we know, 4n was the first reported dithiocarbamate derivative with multifunctional activity. Its excellent profiles in vitro and effectivity in vivo highlight this structurally distinct compound as a potential lead compound in the research of innovative multifunctional drugs for AD.
- Jiang, Neng,Huang, Qichun,Liu, Jing,Liang, Ningsheng,Li, Qing,Li, Qinghua,Xie, Sai-Sai
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- Microwave-Assisted Synthesis of Quinazolines Linked with 1,8-Naphthalimide, Chromene Derivatives and their Antimicrobial Activity
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The synthesis of several quinazolines containing 1,8-Naphthalimide and chromene moieties under conventional and microwave irradiation methods has been reported. The microwave irradiation gave higher yields, shorter reaction time as compared to conventional heating method using green solvents, ecofriendly reaction conditions. All the synthesized compounds were characterized by IR, 1H, 13C NMR, and mass spectral analysis. Furthermore, the titled compounds were screened for their in vitro antimicrobial activity against bacterial strains such as Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, and Escherichia coli as well as fungi such as Aspergillus niger, Aspergillus flavus, and Fusarium oxysporum. Compounds exhibited promising antimicrobial activity.
- Ashok, D.,Dharavath, Ravinder,Nagaraju, Nalaparaju,Ramakrishna, Katta,Reddy, M. Ram,Sarasija, M.
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p. 183 - 189
(2021/08/05)
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- Quinazolone compound and anti-tumor application thereof
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The invention relates to a quinazolone compound and an application thereof in antitumor drugs, and belongs to the technical field of antitumor pharmacy. The technical problem to be solved by the invention is to provide a compound for resisting liver cance
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Paragraph 0014; 0017
(2021/03/06)
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- Coumarin derivatives of - dithiocarbamate and synthesis method thereof
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The invention discloses a coumarin-dithiocarbamate derivative and a synthesizing method thereof. The synthesizing method of the derivative comprises the following steps: 1) utilizing concentrated sulfuric acid as a catalyst, taking resorcinol and ethyl acetoacetate and putting into a first organic solvent to react to obtain an intermediate 2; 2) taking the intermediate 2 and dibromoalkane, puttinginto a second organic solvent and performing reaction under the condition that a pH is larger than or equal to 8 to obtain an intermediate 3; 3) taking the intermediate 3, carbon disulfide and secondary amine, putting into a third organic solvent and performing reaction under the condition that a pH is larger than or equal to 8 to obtain a corresponding target compound crude product. The synthesizing method disclosed by the invention has the advantages of simpleness and easiness in operation, high yield and stable quality; the synthesized coumarin-dithiocarbamate derivative has better acetylcholine esterase inhibiting activity; a lead compound is provided for developing novel AD treating medicine.
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Paragraph 0052-0055
(2020/02/08)
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- Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents
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To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G0/G1 phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis.
- Yu, Haonan,Hou, Zhuang,Tian, Ye,Mou, Yanhua,Guo, Chun
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p. 434 - 449
(2018/04/14)
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- Promising fungicides from allelochemicals: Synthesis of umbelliferone derivatives and their structure–activity relationships
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Umbelliferone was discovered to be an important allelochemical in our previous study, but the contribution of its activity and structure has not yet been revealed. In this study, a series of analogues were synthesized to determine the skeleton of umbelliferone and examine its fungicidal activity. Furthermore, targeted modifications were conducted with three plant parasitic fungi to examine the lead compounds. Among those tested, compounds 2f and 10 were found to show excellent antifungal activity with an inhibitory rate over 80% at 100 ug/mL. The study proves that umbelliferone can be a promising skeleton for fungicides discovery. In addition, the primary structure–activity relationship provides a good guidance for the discovery of novel fungicides based on natural products in the future.
- Pan, Le,Lei, Dongyu,Jin, Lu,He, Yuan,Yang, Qingqing
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- Water-soluble coumarin fluorescent probe as well as preparation method and application thereof
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The invention discloses a water-soluble coumarin fluorescent probe as well as a preparation method and application thereof. The structure of the fluorescent probe is represented by a formula (I) (shown in the description). The probe is capable of selectively identifying mercury ions; and after the probe acts with the mercury ions in a pure water buffer solution, the fluorescence emission at a 450nm site is changed from a hardly any state to 100-time enhanced blue fluorescence, the detection limit to the mercury ions is 0.12mu mol/L, and furthermore, the probe has very strong selectivity and can be used for the naked eye qualitative identification and fluorescent quantitative determination of trace mercury ions.
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Paragraph 0011-0012; 0026-0027
(2017/08/28)
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- Synthesis and evaluation of 7-substituted coumarin derivatives as multimodal monoamine oxidase-B and cholinesterase inhibitors for the treatment of Alzheimer's disease
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A series of 7-substituted coumarin derivatives were designed and synthesised to display ChE and MAO-B inhibitory activity. The compounds consisted out of a coumarin structure (MAO-B inhibitor) and benzyl-, piperidine-, N-benzylpiperidine- or p-bromo-N-benzylpiperizine moiety, resembling the N-benzylpiperidine function of donepezil (ChE inhibitor), connected via an alkyl ether linkage at the 7 position. The biological assay results indicated that all the compounds (1–25) displayed selective inhibition to hMAO-B over hMAO-A, with the benzyloxy series (1–8, 10–13) showing nano-molar hMAO-B inhibition (IC50: 0.5–73?nM). Limited ChE inhibitory activity was however observed for the benzyloxy series with the exception of 2 and especially 3 showing selective BuChE inhibition. From this series 3 showed the best multifunctional activity (eqBuChE IC50?=?0.96?μM, hMAO-A IC50?=?2.13?μM, hMAO-B IC50?=?0.0021?μM). Within the N-benzylpiperidine (16–19) and p-bromo-N-benzylpiperizine (21–24) series the compounds in general showed moderate ChE and MAO-B inhibitory activity. Of these compounds 19 was the most potent multifunctional agent showing good eeAChE and eqBuChE inhibition (IC50?=?9.10?μM and 5.90?μM, respectively), and relatively potent and selective hMAO-B inhibition (IC50?=?0.30?μM, SI?= >33). Molecular modeling revealed that 19 was able to bind simultaneously to the CAS, mid-gorge and PAS sites of AChE and BuChE suggesting that it will be able to inhibit AChE induced Aβ aggregation. From this study, compounds that 3 and 19 can be considered as promising multifunctional lead compounds.
- Joubert, Jacques,Foka, Germaine B.,Repsold, Benjamin P.,Oliver, Douglas W.,Kapp, Erika,Malan, Sarel F.
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p. 853 - 864
(2016/10/26)
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- Design and synthesis of novel coumarin analogs and their nematicidal activity against five phytonematodes
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The presence of hydroxyl groups at the C4 and C7 positions in coumarin backbone has been proposed as a potential modification site for providing excellent bioactivity according to previous studies. A series of novel coumarin derivatives were rationally designed and synthesized by use of a complex catalytic system for a targeted modification at the above sites. These derivatives were assayed for nematicidal activity. As predicted, the derivatization enhanced the activity of the coumarins against five nematodes. Compounds 7b, 9a, 10c and 11c showed significant strong nematicidal broad spectrum activity against all tested nematodes. Compound 10c was the most effective with the lowest LC50 values against Meloidogyne incognita (5.1 μmol/L), Ditylenchus destructor (3.7 μmol/L), Bursaphelenchus mucronatus (6.4 μmol/L), Bursaphelenchus B. xylophilus (2.5 μmol/L) and Aphelenchoides besseyi (3.1 μmol/L), respectively. A brief investigation on the structure-activity relationships (SAR) revealed that the targeted modification by a C7 hydroxyl was optimum compared with that of a C4 hydroxyl and that the coupling chain length was crucial for the nematicidal activity.
- Pan, Le,Li, Xiu-Zhuang,Sun, Di-An,Jin, Hui,Guo, Hong-Ru,Qin, Bo
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supporting information
p. 375 - 379
(2016/03/19)
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- Design, synthesis and cytotoxicity of novel dihydroartemisinin-coumarin hybrids via click chemistry
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In order to develop novel chemotherapeutic agents with potent anticancer activities, we designed four series of novel compounds employing hybridization strategy. Twenty novel dihydroartemisinin-coumarin hybrids, 10a-e, 11a-e, 12a-e, 13a-e, were synthesized via click chemistry in this study and their structures were characterized by HRMS and NMR. The cytotoxic activities were measured by MTT assay against three cancer cell lines (HCT-116, MDA-MB-231, and HT-29) under normoxic or anoxic conditions, respectively. The target compounds exhibited moderate activity with IC50 values in the 0.05-125.40 μM range, and these compounds exhibited better activity against HT-29 cell line under anoxic condition. The cytotoxic activities of most compounds under anoxic condition displayed one- to 10-fold greater activity than under normoxic condition. Compounds 10a - e showed better selectivity against the HT-29 cell line than the other two cell lines. These results indicated that our design of CA IX inhibitors does correspond with its action mode to some degree and deserves further investigation.
- Tian, Ye,Liang, Zhen,Xu, Hang,Mou, Yanhua,Guo, Chun
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- Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease
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Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87 μM and 0.93 μM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37 μM for hAChE; 1.98 μM for hBuChE; 2.62 μM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit.
- Xie, Sai-Sai,Lan, Jin-Shuai,Wang, Xiaobing,Wang, Zhi-Min,Jiang, Neng,Li, Fan,Wu, Jia-Jia,Wang, Jin,Kong, Ling-Yi
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p. 1528 - 1539
(2016/03/16)
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- New coumarin derivative and process for preparing the same
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The present invention refers to the novel coumarin-derivatives and their relates to manufacturing method. Coumarin derivatives the present invention according to and are fluorescent yellow-excellent solubility in an aqueous solution having coumarin havin
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Paragraph 0039; 0052; 0053
(2017/01/31)
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- Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease
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A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BuChE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BuChE (IC50 values of 80.72 nM for eqBuChE and 112.72 nM for hBuChE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 11/4M). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment.
- Xie, Sai-Sai,Wang, Xiaobing,Jiang, Neng,Yu, Wenying,Wang, Kelvin D.G.,Lan, Jin-Shuai,Li, Zhong-Rui,Kong, Ling-Yi
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supporting information
p. 153 - 165
(2015/03/31)
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- Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease
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A series of tacrine-coumarin hybrids (8a-t) were designed, synthesized and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit ChE and self-induced β-amyloid (Aβ) aggregation, and to act as metal chelators. Especially, 8f displayed the greatest ability to inhibit acetylcholinesterase (AChE, IC50 = 0.092 μM) and Aβ aggregation (67.8%, 20 μM). It was also a good butyrylcholinesterase inhibitor (BuChE, IC50 = 0.234 μM) and metal chelator. Besides, kinetic and molecular modeling studies indicated that 8f was a mixed-type inhibitor, binding simultaneously to active, peripheral and mid-gorge sites of AChE. These results suggested that 8f might be an excellent multifunctional agent for AD treatment.
- Xie, Sai-Sai,Wang, Xiao-Bing,Li, Jiang-Yan,Yang, Lei,Kong, Ling-Yi
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p. 540 - 553
(2013/07/27)
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- Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents
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A series of novel 1,2,3-triazole-dithiocarbamate hybrids were designed, synthesized and evaluated for anticancer activity against four selected human tumor cell lines (MGC-803, MCF-7, PC-3, EC-109). Majority of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 3a and 3c showed excellent broad spectrum anticancer activity with IC50 values ranging from 0.73 to 11.61 μM and 0.49-12.45 μM, respectively. Particularly, compound 3a was more potent than 5-fluorouracil against all tested human cancer cell lines. Flow cytometry analysis demonstrated that treatment of MGC-803 with 3c led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death after 12 h.
- Duan, Ying-Chao,Ma, Yong-Cheng,Zhang, En,Shi, Xiao-Jing,Wang, Meng-Meng,Ye, Xian-Wei,Liu, Hong-Min
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- Rational design, synthesis, biological evaluation, homology and docking studies of coumarin derivatives as α1-adrenoceptor antagonists
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According to a three-point pharmacophore for some uro-selective α1-adrenoceptor (AR) antagonists, a novel class of coumarin (=2H-1-benzopyran-2-one) derivatives have been successfully designed and synthesized with high efficacies for α1/s
- Zhou, Xiang,Chen, Ya-Dong,Wang, Tao,Wang, Xiao-Bing,Kong, Ling-Yi
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experimental part
p. 1052 - 1064
(2012/01/06)
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- Etherified 2-hydroxy-ethyl-phosphonic acid derivatives and plant growth regulating agents containing same as active ingredient
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The present invention refers to new etherified hydroxy-alkyl phosphonic acid derivatives of the general formula (I) STR1 wherein R stands for 2,3-dihydro-2,2-dimethyl-benzofuran-7-yl, 4-methyl-coumarin-7-yl, 2,2,4-trimethyl-(2H)-chromen-5-yl or 2,2,4-trimethyl-(2H)-chromen-7,yl, R1 and R2 are the same or different and stand for hydrogen, C1-8 alkyl, C1-4 halogen-alkyl, C1-4 alkoxy-C1-2 alkyl, Me stands for a monovalent cation. The new compounds can be used as active ingredients of plant growth regulating agents.
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