Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antimitotic Agents / pharmacology
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Carbazoles / chemistry*
-
Cell Line, Tumor
-
Chemistry, Pharmaceutical / methods*
-
Drug Design
-
Drug Screening Assays, Antitumor*
-
Humans
-
Inhibitory Concentration 50
-
Ketones / chemistry*
-
Models, Chemical
-
Structure-Activity Relationship
-
Sulfonamides / chemistry*
-
Tubulin / chemistry
Substances
-
Antimitotic Agents
-
Antineoplastic Agents
-
Carbazoles
-
Ketones
-
Sulfonamides
-
Tubulin