- Discovery of isoliquiritigenin analogues that reverse acute hepatitis by inhibiting macrophage polarization
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Screening a natural product library of 850 compounds yield isoliquiritigenin as an effective anti-inflammatory agent by inhibiting the production of pro-inflammatory NO induced by Pam3CSK4, while its activity accompanied by toxicity. Further studies obtained the optimized isoliquiritigenin derivative SMU-B14, which can inhibit Pam3CSK4 triggered toll-like receptor 2 (TLR2) signaling with low toxicity and high potency. Preliminary mechanism studies indicated that SMU-B14 worked through TLR2/MyD88, phosphorylation of IKKα/β, leading to the reduce degradation of NF-κB related IKBα and p65 complex, then inhibited the production of inflammatory cytokines, such as TNF-α, IL-6, IL-1β both in human and murine cell lines. Subsequent polarization experiments showed SMU-B14 significant reversed the polarization of M1 phenotype primary macrophage activated by Pam3CSK4 in vitro, and reduced the infiltration of neutrophil and polarization of M1-type macrophage, decreased serum alanine transaminase (ALT), as a result protected liver from being injured in vivo. In summary, we obtained an optimized lead compound SMU-B14 and found it functionally blocked TLR2/MyD88/NF-κB signaling pathway to down-regulate the production of inflammatory cytokines resulted significant liver protection property.
- Yang, Junjie,Hu, Fanjie,Guo, Chengjun,Liang, Yuqing,Song, Haiying,Cheng, Kui
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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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- Facile formation of methylenebis(chalcone)s through unprecedented methylenation reaction. Application to antiparasitic and natural product synthesis
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The formation of methylenebis(chalcone)s has been discovered during deprotection with methoxymethyl groups from trihydroxychalcones. Studies on this methylenation reaction led to a mechanism hypothesis that was extended to other chalcones and to dihydrochalcone, acetophenone, benzophenone and flavone derivatives. This new method was applied to the rapid synthesis of natural product piperanduncin C. These original methylenebis compounds were also evaluated for their antiparasitic activity. Copyright
- Thevenin, Marion,Mouray, Elisabeth,Grellier, Philippe,Dubois, Joelle
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p. 2986 - 2992
(2014/05/20)
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- COMPOUNDS, THEIR SYNTHESES, AND THEIR USES
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Embodiments of the present invention provide compounds (such as Formula (I) compounds, Formula (II) compounds, and various embodiments thereof). Compositions comprising those compounds are also provided. Methods for their preparation are included. Also, uses of the compounds are included, such as administering and treating diseases (e.g., cancer and infections).
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Page/Page column 46
(2010/04/03)
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- In vitro and in vivo anti-Leishmania activity of polysubstituted synthetic chalcones
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The in vitro screening of 43 polysubstituted chalcones against Leishmania amazonensis axenic amastigotes, led to the evaluation of 9 of them in a macrophage-infected model with the two other most infectious Leishmania species prevalent in Peru (L. braziliensis and L. peruviana). The five most active and selective chalcones were studied in vivo, resulting on the identification of two chalcones with high reduction parasite burden percentages.
- Aponte, Jose C.,Castillo, Denis,Estevez, Yannick,Gonzalez, German,Arevalo, Jorge,Hammond, Gerald B.,Sauvain, Michel
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supporting information; experimental part
p. 100 - 103
(2010/04/06)
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- Syntheses of Two New Naturally Occurring Dihydrochalkones, Uvangolatin and 2',4'-Dihydroxy-4,6'-dimethoxydihydrochalkone
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The structures proposed for the two naturally occurring dihydrochalkones, uvangolatin isolated from Uvaria angolensis as 2',4'-dihydroxy-6'-methoxydihydrochalkone (I) and another dihydrochalkone isolated from Iryanthera laevis as 2',4'-dihydroxy-4,6'-dime
- Bhardwaj, D. K.,Jain, R. K.,Munjal, Anita,Prashar, Meenu
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p. 476 - 477
(2007/10/02)
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