Among the topoisomerases, DNA gyrase belongs to the type II classes that catalysing DNA supercoiling or relaxation,
catenation or decatenation, knotting or unknotting. It is one of the validated targets for anti-tubercular drug discovery
and inhibitors from this group are also active against non-replicating, persistent mycobacteria, which might be important
for shortening the duration of TB therapy. From past few years, extensive research was carried out towards potent
DNA gyrase inhibitor design. The current review focuses on the most of potent series of DNA gyrase inhibitors and its
structure activity relationships (SAR). The current manuscript also reports the current research on identification of potent
DNA gyrase inhibitors using ligand based virtual screening approaches. The pharmacophore model was developed and
validated against 65 known Mycobacterium smegmatics (MS) DNA Gyrase inhibitors. Validated pharmacophore model
consists of HBA, HY, and RA features were essential for DNA Gyrase inhibition and this model was used to screen virtual
screening to retrieve potential inhibitors from our in house database. Finally, 15 hits were ranked as potential leads
based on pharmacophoric fit value and estimated activity. Furthermore, in-vitro enzymatic inhibition studies were performed
for these 15 most promising candidates and these compounds were found to exhibit inhibition at 30µM.
Keywords: DNA gyrase, HypoGen, mycobacterium smegmatics, pharmacophore, QSAR, virtual screening.
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