Identification of potential inhibitor targeting enoyl-acyl carrier protein reductase (InhA) in Mycobacterium tuberculosis: a computational approach.
The explosive global spreading of multidrug resistant Mycobacterium tuberculosis (Mtb) has provoked an urgent need to discover novel anti-TB agents. Enoyl-acyl carrier protein reductase from Mtb is a well-known and thoroughly studied target for anti-tuberculosis therapy. In the present analysis, virtual screening techniques performed from Drug bank database by utilizing INH-NAD adduct as query for the discovery of potent anti-TB agents. About 100 molecules sharing similar scaffold with INH-NAD adduct were analyzed for their binding effectiveness. The initial screening based on number of rotatable bonds gave 42 hit molecules. Subsequently, physiochemical properties such as toxicity, solubility, drug-likeness and drug score were analyzed for the filtered set of compounds. Final data reduction was performed by means of molecular docking and normal mode docking analysis. The result indicates that DB04362, adenosine diphosphate 5-(beta-ethyl)-4-methyl-thiazole-2-carboxylic acid could be a promising lead compound and be effective in treating sensitive as well as drug-resistant strains of Mtb. We believe that this novel scaffolds might be the good starting point for lead compounds and certainly aid the experimental designing of anti-tuberculosis drug in a short time.
Industrial Biotechnology Division, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India. shanthi.v@vit.ac.in.
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Shanthi
Bioinformatics Division, School of Bio Sciences and Technology, VIT University, Vellore, 632014, Tamil Nadu, India.
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Ramanathan
Bioavailability; INH-NAD adduct; Molecular docking; Normal mode analysis; Virtual screening