Insights into development of Decaprenyl-phosphoryl-β-D-ribose 2'-epimerase (DprE1) inhibitors as antitubercular agents: A state of the art review

Abstract

Mycobacterium tuberculosis is a causative agent for the world threatening infectious disease known as tuberculosis. M. tuberculosis is also referred as Koch's bacillus as it was first defined by Robert Koch in 1821. In the entire history of M. tuberculosis infection, several different targets were identified and explored with a hope of effective therapeutic treatment against tuberculosis. Drug-resistant tuberculosis is the major obstacle for researchers and letting them fail continuously to discover new drug candidates. Among the numerous antitubercular targets, Decaprenyl-phosphoryl-β-D-ribose-2'-epimerase (DprE1) is novel target identified in the year 2009. The present article portrays insights of DprE1 enzyme in all the aspects i.e., identification, structural elucidation to designing strategies and synthesis of potential drug candidates to combat resistant strains. Along with the synthesis and biological activity of novel compounds, structure-activity relationship (SAR) data is given to help medicinal chemists and researchers working in this area for the development of new inhibitors to fight against M. tuberculosis. DprE1 is new ray of hope for antitubercular treatment. No single drug candidate (DprE1 inhibitor) has passed clinical trial yet and hence it nullifies the risk of development of resistance or mutations at specific residues. Researchers working in this area have to design and come up with new potent candidates with less dose, no toxicity to combat this deadly infection. This review emphasized on year wise systematic development and progress of DprE1 inhibitors.

Keywords: Antitubercular drug discovery; DprE1 inhibitors; SAR; Systematic development; Tuberculosis.