Design,Synthesis and Cytotoxicity of Thiazole-Based Stilbene Analogs as Novel DNA Topoisomerase IB Inhibitors |
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| Authors: | Jin-Chuan Liu Bo Chen Jia-Lin Yang Jian-Quan Weng Qian Yu De-Xuan Hu |
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| Institution: | 1.College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China; (J.-C.L.); (B.C.); (J.-L.Y.);2.School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China;3.School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; |
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| Abstract: | A series of new thiazole-based stilbene analogs were designed, synthesized and evaluated for DNA topoisomerase IB (Top1) inhibitory activity. Top1-mediated relaxation assays showed that the synthesized compounds possessed variable Top1 inhibitory activity. Among them, (E)-2-(3-methylstyryl)-4-(4-fluorophenyl)thiazole (8) acted as a potent Top1 inhibitor with high Top1 inhibition of ++++ which is comparable to that of CPT. A possible binding mode of compound 8 with Top1–DNA complex was further provided by molecular docking. An MTT assay against human breast cancer (MCF-7) and human colon cancer (HCT116) cell lines revealed that the majority of these compounds showed high cytotoxicity, with IC50 values at micromolar concentrations. Compounds 8 and (E)-2-(4-tert-butylstyryl)-4-(4-fluorophenyl)thiazole (11) exhibited the most potent cytotoxicity with IC50 values of 0.78 and 0.62 μM against MCF-7 and HCT116, respectively. Moreover, the preliminary structure–activity relationships of thiazole-based stilbene analogs was also discussed. |
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| Keywords: | thiazole-based stilbene analogs topoisomerase IB inhibitor cytotoxicity |
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