Diversity-oriented synthesis for novel, selective and drug-like inhibitors for a phosphatase from Mycobacterium tuberculosis

Abstract

Mycobacterium protein tyrosine phosphatase B (mPTPB) is a potential drug target of tuberculosis (TB). Using small molecule inhibitors of mPTPB could be a treatment to overcome emerging TB drug resistance. Using a Diversity-Oriented Synthesis (DOS) strategy, we successfully developed a salicylic acid based and drug-like mPTPB inhibitor with an IC₅₀ of 2 μM and >20-fold specificity over many human PTPs, making it an excellent lead molecule for anti-TB drug discovery. In addition, DOS generated bicyclic salicylic acids are also promising starting points for acquiring inhibitors targeting other PTPs.