Novel potent antimitotic heterocyclic ketones: synthesis, antiproliferative activity, and structure-activity relationships.
We report the synthesis, antiproliferative activity, and SAR of novel heterocyclic ketones derived from carbazole sulfonamides. Most of the heterocyclic ketones showed strong cytotoxicities. (N-1-Methylindole-5-yl)-(3,4,5-trimethoxyphenyl)-methanone 8b gave the most potent cytotoxicity (9.2-26 nM) against seven human tumor cell lines. The mechanism of action of the heterocyclic ketones appears to involve targeting of tubulin, similar to that of CA-4 and different from the carbazole sulfonamides.
Hu
Laixing
L
Department of Chemistry, Georgia State University, Atlanta, GA 30303-3083, USA.
Jiang
Jian-dong
JD
Qu
Jinrong
J
Li
Yan
Y
Jin
Jie
J
Li
Zhuo-rong
ZR
Boykin
David W
DW
D050256:Antimitotic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry*; D014404:Tubulin / Q000737:chemistry
D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D002227:Carbazoles; D007659:Ketones; D013449:Sulfonamides; D014404:Tubulin