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4,5‐Diaryl‐3‐aminopyrazole Derivatives as Analogs of Combretastatin A‐4: Synthesis and Biological Evaluation
Author(s) -
Liu Tao,
Cui Rong,
Chen Jing,
Zhang Jun,
He Qiaojun,
Yang Bo,
Hu Yongzhou
Publication year - 2011
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.201000069
Subject(s) - combretastatin , cytotoxicity , chemistry , tubulin , stereochemistry , docking (animal) , cell culture , biological activity , chemical synthesis , k562 cells , cell cycle , microtubule , cell , biochemistry , in vitro , biology , medicine , genetics , nursing , microbiology and biotechnology
Abstract A series of cis ‐restricted 4,5‐diaryl‐3‐aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitr o against five human cancer cell lines (K562, ECA‐109, A549, SMMC‐7721, and PC‐3). Compounds 5a , 5b , 5d , and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G 2 /M phase. The docking research showed the conformation of 5a overlaps well with CA‐4 in the crystallized protein complex, suggesting the 4,5‐diaryl‐3‐aminopyrazoles were good mimics of CA‐4.