Design, synthesis, and biological evaluation of novel N-γ-carboline arylsulfonamides as anticancer agents.
A series of novel N-γ-carboline arylsulfonamide derivatives designed based on the common feature of colchicine binding site inhibitors were synthesized and evaluated for their antiproliferative activity in vitro against five human cancer cell lines. Most of the compounds showed moderate to potent cytotoxic activities against all the tested cells. Preliminary mechanism research on one of the most potent compound 6p indicated that it was a potent tubulin polymerization inhibitor, with IC(50) value of 3.8 μM, equivalent to that of CA-4, and arresting cell cycle in G(2)/M phase.
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 Zhejiang, China.
Jing
J
Chen
Tao
T
Liu
Rui
R
Wu
Jianshu
J
Lou
Ji
J
Cao
Xiaowu
X
Dong
Bo
B
Yang
Qiaojun
Q
He
Yongzhou
Y
Hu
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D002243:Carbolines; D013449:Sulfonamides; D050257:Tubulin Modulators; C055572:gamma-carboline; D003078:Colchicine