Discovery of Low Nanomolar and Subnanomolar Inhibitors of the Mycobacterial beta-Carbonic Anhydrases Rv1284 and Rv3273


Guzel O., Maresca A., Scozzafava A., Salman A., Balaban A. T., Supuran C. T.

JOURNAL OF MEDICINAL CHEMISTRY, vol.52, no.13, pp.4063-4067, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 52 Issue: 13
  • Publication Date: 2009
  • Doi Number: 10.1021/jm9004016
  • Journal Name: JOURNAL OF MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.4063-4067
  • Istanbul University Affiliated: Yes

Abstract

A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate, leading to pyridinium derivatives. The new sulfonamides were evaluated as inhibitors of two beta-carbonic anhydrases (CAs, EC 4.2.1.1) from Mycobaterium tuberculosis, Rv1284 and Rv3273. The whole series showed excellent nanomolar inhibitory activity, with several subnanomolar inhibitors being detected. Rv1284 and Rv3273 have potential for developing antimycobacterial agents with an alternate mechanism of action.