Non-classical beta-carbonic anhydrase inhibitors-towards novel anti-mycobacterials
Natascha von Gnielinski, Lisa Nienaber, Lyndel Mason, Samantha Ellis, James A Triccas, Rohan A Davis, Andreas Hofmann
MEDCHEMCOMM | ROYAL SOC CHEMISTRY | Published : 2014
Mycobacterial carbonic anhydrases, such as the essential protein Rv3588c, are attractive drug targets since they constitute a different class of carbonic anhydrases than those found in humans. A natural product library has been screened for compounds that inhibit mycobacterial carbonic anhydrases but lack the much-exploited sulfonamide/sulfamate group. The identified inhibitors of mycobacterial Rv3588c are likely to affect the enzyme at a site different from the catalytic centre-a concept which may be exploited for novel specific anti-mycobacterials. This journal is
We gratefully acknowledge A. Jones and A. Suarez Covarrubias (Uppsala) for sharing their His<INF>6</INF>-Rv1284 and His<INF>6</INF>-Rv3588c expression plasmids, and R. Quinn for access to the sponge samples (sources of 1 and 2). Research in the labs of AH and PAD is funded by the National Health and Medical Research Council and the Australian Research Council.