Docking Studies, Synthesis, SAR and Anti-TB Activity of Glycinamido Analogues

Abstract

Mycolic acid is a crucial component of the Mycobacterium tuberculosis cell wall and mycolic acid methyltransferases (MAMTs) are essential for mycolic acids to mature. In the present study, an inhouse library of 330 ligands was designed taking glycinamido moiety as scaffold. Virtual screening was carried out with this library of compounds against MmaA1 as the target protein. About 55 hits were identified through docking, ADMET studies and these molecules were synthesized by the Schotten-Baumann reaction followed by a nucleophilic substitution reaction. All the compounds were subjected to in vitro anti-Tb screening by microplate alamar blue assay (MABA). The Mdb1, Mdb4 & Meb1 exhibited excellent activity against M. tuberculosis H37Rv bacilli strain with an MIC of 1.56 µg/mL. The SAR studies shows that the aryl ring attached directly to the nitrogen atom as present in 2(-N-substituted glycinamido) derivatives is essential for the compound to exhibit potent anti-TB activity.