LC-MS Based Approach to Characterize Non-Specific Binding Inhibitors to Mycobacterium tuberculosis Shikimate Kinase (MtSK)

摘要

The emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) increased the demand for the discovery of new antitubercular drugs. The shikimate pathway in (Mt) is essential for its survival, due to the production of chorismate, a precursor for aromatic amino acids but absent from mammals. Shikimate kinase (SK) is the fifth enzyme that catalyzes a phosphate transfer from ATP to shikimate, producing shikimate-3-phosphate (S3P) and ADP, it has been considered a promising drug target for tuberculosis drug discovery. The goal of this study is to understand the inhibitory mechanism of the most active compounds from a set of 14 oxadiazole-amide and 2-aminobenzothiazole containing synthetic compounds with IC50 value <50 μM against MtSK using an LC-MS based approach.