Pharmacophore-based Screening of Antimycobacterial 2-Pyrone-Tethered Nitrobenzothiazinone

Rational and structure-based drug design is more efficient than the traditional method of drug discovery because this method examines the molecular basis of disease and uses the three-dimensional structure of the biological target. A series of 2-pyrone derivatives of Nitrobenzothiazinone were developed and evaluated for their drug-likeness, solubilities and pharmacokinetic and pharmacodynamic data employing two free software packages (SwissADME and admetSAR). The compounds were further evaluated for their binding affinities against DprE1, an essential enzyme involved in fatty acid biosynthesis, leading to cell death of Mycobacterium tuberculosis (M. tuberculosis) and three of compounds showed affinities higher than 5 nitrobenzothiazinone. Virtual screening showed a high molecular similarity (<90%) between the developed ligands. The potential of 2-pyrone-tethered Nitrobenzothiazinone towards DprE1 indicates the need for further evaluation in animal studies against both M. tuberculosis and other non-tuberculous Mycobacteria.