DprE1 inhibitors: An insight into the recent developments and synthetic approaches

In the current medical era, the proliferation and dissemination of drug-resistant strains of Mycobacterium tuberculosis (Mtb) continue to pose a significant worldwide health hazard, necessitating the development of new and innovative medications to combat tuberculosis. Decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1) is a crucial enzyme for cell wall synthesis in Mtb. Its importance is due to its eminent contribution in forming lipoarabinomannan and arabinogalactan, key components of the mycobacterial cell wall. The emergence of the DprE1 enzyme as a druggable target was based on inhibitors discovered in high-throughput screening. Since then, inhibitors with different types of chemical scaffolds have been reported for their activity against it. DprE1 inhibitors can be categorized according to the formation of a covalent or non-covalent bond in the enzyme's active site, causing a loss of its catalytic activity, leading to Mtb's demise. Herein, we describe diverse DprE1 inhibitors that have had anti-tubercular activity reported over the past fifteen years and till the present time.