Inhibitors of Inosine 5´-monophosphate dehydrogenase as emerging new age antimicrobial agents
Inosine 5´-monophosphate dehydrogenase (IMPDH) is a vital enzyme involved in the de-novo synthesis of guanine nucleotides. IMPDH catalyses a crucial step of converting IMP into XMP that is further converted into GMP. Microbial infections rely on the rapid proliferation of the bacteria, this requires the rate-limiting enzyme IMPDH to expand the guanine nucleotide pool and hence IMPDH has recently received lots of attention as a potential target for treating infections. Owing to the structural and kinetic differences in the host IMPDH and bacterial IMPDH a selective targeting is possible and is a crucial feature in the development of new potent and selective inhibitors of bacterial IMPDH. The earlier screening of small molecules revealed a structural requirement for the bacterial/protozoal IMPDH. Early optimisation of benzimidazole and benzoxazole scaffold led to discovery of new potent and selective inhibitors of pathogenic IMPDH. Further research is vastly focused on the development of highly potent and selective inhibitors of various bacterial IMPDHs. Such studies reveal the importance of this excellent target for treating infectious diseases. The current review focus on the recent developments in the discovery and development of selective inhibitors of bacterial/protozoal IMPDH with emphasis on the inhibition mechanism and structure activity relationship.