1587732-61-3Relevant articles and documents
Discovery and structure optimization of a series of isatin derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors
Jeankumar, Variam U.,Alokam, Reshma,Sridevi, Jonnalagadda P.,Suryadevara, Priyanka,Matikonda, Siddharth S.,Peddi, Santosh,Sahithi, Seedarala,Alvala, Mallika,Yogeeswari, Perumal,Sriram, Dharmarajan
, p. 498 - 506 (2014)
In this study, the crystal structure of the Mycobacterium tuberculosis (MTB) enzyme chorismate mutase (CM) bound to transition state analogue (PDB: 2FP2) was used as a framework for virtual screening of the BITS-Pilani in-house database (2500 compounds) to identify new scaffold. We identified isatin as novel small molecule MTB CM inhibitors; further twenty-four isatin derivatives were synthesized and evaluated in vitro for their ability to inhibit MTB CM, and activity against M. tuberculosis as steps towards the derivation of structure-activity relationships (SAR) and lead optimization. Compound 3-(4-nitrobenzylidene)indolin-2-one, 24 emerged as the most promising lead with an IC50 of 1.01 ± 0.22 μm for purified CM and MIC of 23.5 μm for M. tuberculosis, with little or no cytotoxicity. 2D interaction profile of compounds 1, 7 and 25 with the active site residues.