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, cilt.52, ss.4063-4067, 2009 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 52 Konu: 13
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1021/jm9004016
  • Dergi Adı: JOURNAL OF MEDICINAL CHEMISTRY
  • Sayfa Sayıları: ss.4063-4067

Özet

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.