1,3,4-Oxadiazole derivatives as potential antitumor agents:discovery,optimization and biological act

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  Recent studies have proved that focal adhesion kinase(FAK)is a new potential therapeutic target in cancer therapy.In this study,a virtual scraening was conducted to discover potentia[ candidates for FAK inhibitors.Based on the results.a series of novel oxadiazole derivatives(5a-5q)bearrng the benzotriazole group were designed and synthesized for FAK inhibitory evaluation.Among the compounds.5h,which has an ortho methoxy group on the benzene ring.exhibited the most potent inhibitory activity for cancer cell growth with an IC50 value of 11 μM and 0.250 μM against Hela cells and FAK.respectively.Further,the apoptosis assay indicated that compound 5h induced the apoptosis of HeLa cells,and docking simulation showed that 5h could bind to the FAK protein catalytic region.Taking these together.5h could be a lead for discovering novel FAK inhibitors.
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