Design, Synthesis, Characterization of Novel Sulfathiazole Derivatives and their in silico and in vitro Analysis against Multidrug-Resistance Tuberculosis using Docking Studies

Abstract

In this study, seven novel sulfathiazole derivatives were synthesized from sulfathiazole using different substituted aldehydes and characterized by IR, NMR and LC-MS analysis. Using molecular docking and toxicity prediction, all the seven novel sulfathiazole derivatives (Mol-14, Mol-15, Mol-21, Mol-27, Mol-36, Mol-39 and Mol-43) were virtually screened from generated 70 compounds and assessed their effectiveness against multidrug resistant Mycobacterium tuberculosis (MDR-TB). The Inha protein of TB were performed and all the compounds found to have good docking scores in the range of -7.2 to -9.1 Kcal/mol. Compound, 4-(4-oxo-2-phenyl-1,3-thiazolidin-3-yl)-N-(1,3-thiazol-2-yl)benzene-1- sulfonamide (Mol-27) shown to inhibit the MDR-TB and wild-type TB strain with an MIC value of 1 μg/mL and 0.25, respectively. The standard sulfathiazole and isoniazid were compared to the minimal inhibitory concentration (MIC) of the synthesized Mol-14, Mol-15, Mol-21, Mol-27, Mol-36, Mol-39 and Mol-43 new sulfathiazole derivatives. Based on the results, these compounds shows promising activity against MDR-TB.