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

Article Details

Citation
Copy to clipboard

Guzel O, Maresca A, Scozzafava A, Salman A, Balaban AT, Supuran CT

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.

PubMed ID
19438226 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AcetazolamideCarbonic anhydrase 1Ki (nM)481N/AN/ADetails
AcetazolamideCarbonic anhydrase 2Ki (nM)104N/AN/ADetails