Abstract
In our previous work, some promising hits for Mtb-ASADH were identified using pharmacoinformatics approaches. Total ten compounds were selected for biological evaluation against Mtb- ASADH, nine of these were selected from virtual screening employing shape based and pharmacophore models and remaining one was designed from analog design. Cysteine has been reported as a covalently bonded inhibitor for Mtb-ASADH in a crystal structure (PDB ID: 3TZ6). Six out of ten compounds showed good inhibition of Mtb-ASADH. All these six molecules ZINC00108239, ZINC36358489, NSC4862, NSC109187, NSC51108, NSC226144 and S-carboxymethyl-L-cysteine showed IC50 values ranging from 65-100 µM. The binding mode analysis of S-carboxymethyl-L-cysteine, which showed highest inhibitory activity among tested compounds, exhibited binding interactions with catalytic residues Arg99, Arg249, Lys227 and His256. These studies can be further exploited for lead optimization and rational drug designing to find new leads against Tuberculosis.
Keywords: Mtb-ASADH, biological evaluation, S-carboxymethyl-L-cysteine, pharmacoinformatics, molecular docking.
Graphical Abstract
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