Discovery of low nanomolar and subnanomolar inhibitors of the mycobacterial beta-carbonic anhydrases Rv1284 and Rv3273.
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 Mycobacterium 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.
Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116 Beyazit, Istanbul, Turkey.
Ozlen
O
Güzel
Alfonso
A
Maresca
Andrea
A
Scozzafava
Aydin
A
Salman
Alexandru T
AT
Balaban
Claudiu T
CT
Supuran
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002257:Carbonic Anhydrase Inhibitors; D011725:Pyridines; D013449:Sulfonamides