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Synthesis and Biological Evaluation of 1‐Phenyl‐1,2,3,4‐dihydroisoquinoline Compounds as Tubulin Polymerization Inhibitors
Author(s) -
Zheng CanHui,
Chen Jun,
Liu Jia,
Zhou XiaoTian,
Liu Na,
Shi Duo,
Huang JingJing,
Lv JiaGuo,
Zhu Ju,
Zhou YouJun
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201100169
Subject(s) - isoquinoline , chemistry , tubulin , stereochemistry , polymerization , cytotoxicity , biological activity , docking (animal) , microtubule , combinatorial chemistry , in vitro , organic chemistry , biochemistry , polymer , medicine , nursing , biology , microbiology and biotechnology
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.