Premium
Synthesis and Biological Evaluation of Benzothiazole Derivatives Bearing the ortho ‐Hydroxy‐ N ‐acylhydrazone Moiety as Potent Antitumor Agents
Author(s) -
Ma Junjie,
Zhang Guangyan,
Han Xiaoqi,
Bao Guanglong,
Wang Lihui,
Zhai Xin,
Gong Ping
Publication year - 2014
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.201400230
Subject(s) - moiety , benzothiazole , chemistry , stereochemistry , cytotoxicity , biological activity , kinase , ring (chemistry) , structure–activity relationship , in vitro , biochemistry , organic chemistry
A novel series of benzothiazole derivatives bearing the ortho ‐hydroxy‐ N ‐acylhydrazone moiety were designed, synthesized, and evaluated for their procaspase‐3 kinase activation activities and antiproliferative activities against five cancer cell lines (NCI‐H226, SK‐N‐SH, HT29, MKN‐45, and MDA‐MB‐231). Most target compounds showed moderate to excellent cytotoxic activity against all five tested cancer lines. The most promising compound 18e (procaspase‐3 EC 50 = 0.31 µM) with IC 50 values ranging from 0.24 to 0.92µM against all tested cell lines was 4.24–12.2 times more active than PAC‐1 (procaspase‐3 EC 50 = 0.41 µM). Structure–activity relationship studies indicated that the phenyl group on the 2‐hydroxyphenyl ring (moiety A) was critical for pharmacological activity in vitro . In addition, introduction of a benzyloxyl group on moiety A and a mono‐electron‐withdrawing group at the 4‐position of the benzyloxyl group were more favorable for antitumor activity. Moreover, reduction of the electron density in the phenyl ring of the benzyloxy group led to a dramatic decrease in the procaspase‐3 kinase activation activity.