Synthesis and biological evaluation of 1-phenyl-1,2,3,4-dihydroisoquinoline compounds as tubulin polymerization inhibitors |
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Authors: | Zheng Can-Hui Chen Jun Liu Jia Zhou Xiao-Tian Liu Na Shi Duo Huang Jing-Jing Lv Jia-Guo Zhu Ju Zhou You-Jun |
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Institution: | School of Pharmacy, Second Military Medical University, Shanghai, China. |
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Abstract: | A series of 1-phenyl-3,4-dihydroisoquinoline derivatives and several 1-phenyl-1,2,3,4-tetrahydroisoquinoline, 1-phenyl-isoquinoline analogues were synthesized, and their cytotoxicity and tubulin polymerization inhibitory activity were evaluated. The 1-phenyl-3,4-dihydroisoquinoline compounds were found to be potential tubulin polymerization inhibitors. Compound 5n, bearing a 3'-OH and 4'-OCH(3) substituted 1-phenyl B-ring, was shown to confer optimal bioactivity. The single-crystal structure of 5n was further determined by X-ray diffraction, and the binding mode of 5n to tubulin was obtained by molecular docking, which can explain the structure-activity relationships. The studies presented here provide a new structural type for the development of novel antitumor agents. |
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Keywords: | 1‐Phenyl‐1 2 3 4‐dihydroisoquinoline Antitumor agent Tubulin polymerization inhibitor |
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