Design and development of new class of Mycobacterium tuberculosis l-alanine dehydrogenase inhibitors

Add time:08/12/2019    Source:sciencedirect.com

Mycobacterium tuberculosis l-alanine dehydrogenase (MTB l-AlaDH) is one of the important drug targets for treating latent/persistent tuberculosis. In this study we used crystal structure of the MTB l-AlaDH bound with cofactor NAD+ as a structural framework for virtual screening of our in-house database to identified new classes of l-AlaDH inhibitor. We identified azetidine-2,4-dicarboxamide derivative as one of the potent inhibitor with IC50 of 9.22 ± 0.72 μM. Further lead optimization by synthesis leads to compound 1-(isonicotinamido)-N2,N4-bis(benzo[d]thiazol-2-yl)azetidine-2,4-dicarboxamide (18) with l-AlaDH IC50 of 3.83 ± 0.12 μM, 2.0 log reduction in nutrient starved dormant MTB model and MIC of 11.81 μM in actively replicative MTB.

We also recommend Trading Suppliers and Manufacturers of alanine 2,6-dichlorophenyl ester (cas 113366-34-0). Pls Click Website Link as below: cas 113366-34-0 suppliers

Prev:Penetration into and exposure of Cefozopran (cas 113359-04-9) in pelvic retroperitoneal space exudate
Next:N-Sulfamoylphenyl- and N-sulfamoylphenyl-N-thiazolyl-β-alanines and their derivatives as inhibitors of human carbonic anhydrases)