Premium
Design, synthesis and biological evaluation of benz‐fused five‐membered heterocyclic compounds as tubulin polymerization inhibitors with anticancer activities
Author(s) -
Komuraiah Buduma,
Ren Yichang,
Xue Mingming,
Cheng Binbin,
Liu Jin,
Liu Yao,
Chen Jianjun
Publication year - 2021
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13832
Subject(s) - tubulin , in vitro , chemistry , colchicine , microtubule , stereochemistry , cell cycle , polymerization , combinatorial chemistry , cancer cell , cell culture , biochemistry , cancer , cell , biology , polymer , organic chemistry , microbiology and biotechnology , genetics
A series of benz‐fused five‐membered heterocyclic compounds were designed and synthesized as novel tubulin inhibitors targeting the colchicine binding site. Among them, compound 4d displayed the highest antiproliferative activity against four cancer cell lines with an IC 50 value of 4.9 μM in B16‐F10 cells. Compound 4d effectively inhibited tubulin polymerization in vitro (IC 50 of 13.1 μM). Further, 4d induced cell cycle arrest in G2/M phase. Finally, 4d inhibited the migration of cancer cells in a dose‐dependent manner. In summary, these results suggest that compound 4d represents a new class of tubulin inhibitors deserving further investigation.