A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

A high-throughput screen against pantothenate synthetase (PanC) identifies 3-biphenyl-4-cyanopyrrole-2-carboxylic acids as a new class of inhibitor with activity against Mycobacterium tuberculosis.

Blog Article

The enzyme pantothenate synthetase, PanC, is an attractive drug target in Mycobacterium tuberculosis.It is essential for the in vitro growth of M.tuberculosis and for survival of the bacteria in the biomat for sale mouse model of infection.PanC is absent from mammals.

We developed an enzyme-based assay to identify inhibitors of PanC, optimized it for high-throughput screening, and tested a large and diverse library of compounds for activity.Two compounds belonging to the same chemical class of 3-biphenyl-4- cyanopyrrole-2-carboxylic acids had activity against the purified recombinant protein, and also inhibited att nighthawk hotspot growth of live M.tuberculosis in manner consistent with PanC inhibition.Thus we have identified a new class of PanC inhibitors with whole cell activity that can be further developed.