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). 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.

• Authors: Rongjun He, Yunpeng Bai, Zhi-Hong Yu, Li Wu, Andrea Michelle Gunawan, Zhong-Yin Zhang
• Journal: MedChemComm (Medchemcomm) Vol. 5 Issue 10 Pg. 1496-1499 (Oct 2014) ISSN: 2040-2503 [Print] England
• PMID: 25505942 (Publication Type: Journal Article)