Discovery of low nanomolar and subnanomolar inhibitors of the mycobacterial beta-carbonic anhydrases Rv1284 and Rv3273

Ozlen Güzel; Alfonso Maresca; Andrea Scozzafava; Aydin Salman; Alexandru T Balaban; Claudiu T Supuran

doi:10.1021/jm9004016

Discovery of low nanomolar and subnanomolar inhibitors of the mycobacterial beta-carbonic anhydrases Rv1284 and Rv3273

J Med Chem. 2009 Jul 9;52(13):4063-7. doi: 10.1021/jm9004016.

Authors

Ozlen Güzel¹, Alfonso Maresca, Andrea Scozzafava, Aydin Salman, Alexandru T Balaban, Claudiu T Supuran

Affiliation

¹ Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 34116 Beyazit, Istanbul, Turkey.

PMID: 19438226
DOI: 10.1021/jm9004016

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 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / pharmacology
Bacterial Proteins / antagonists & inhibitors
Carbonic Anhydrase Inhibitors / chemical synthesis*
Carbonic Anhydrase Inhibitors / pharmacology
Mycobacterium tuberculosis / drug effects
Pyridines / chemical synthesis
Pyridines / pharmacology
Sulfonamides / chemical synthesis*
Sulfonamides / chemistry
Sulfonamides / pharmacology

Substances

Anti-Bacterial Agents
Bacterial Proteins
Carbonic Anhydrase Inhibitors
Pyridines
Sulfonamides