In - Silico Studies of Thiopyridine Compounds as Anti - Bacterial Agents Targeting Enoyl -  Acyl Carrier Protein Reductase

Meenambiga Setti Sudharsan^1*, Sandra Jose¹, Sowmya Hari¹ , Venkataraghavan Ragunathan² and Sakthiselvan Punniavan¹

¹Department of Bio-Engineering, School of Engineering, Vels Institute of Science Technology and Advanced Studies, Chennai-600117, Tamil Nadu, India

²Department of Chemical Engineering, Alagappa College of Technology, Anna University, Chennai-600025.

Corresponding Author E-mail: meenambiga.se@velsuniv.ac.in

DOI : http://dx.doi.org/10.13005/bbra/2962

ABSTRACT:

In the Fatty Acid Synthase II system, Enoyl-(acyl-carrier-protein) reductase (ENR) encoded by FabI genes is a limiting step enzyme and there is no homologue ENR found in invertebrates which makes it selective target for drug discovery. From Molecular dynamics simulations it was concluded that the solvated protein stabilized at 2.5 ns with larger mobility in the substrate - binding loop and the conformational flexibility of the molecule was revealed. To study the inhibitory effects of novel small molecules in the thiopyridine series, a 2D QSAR model was developed and evaluated for its efficiency. The R² > 0.96 and Q² = 0.978 depicted the predictive ability of the models which was determined using a test set of 3 compounds. The receptor-ligand interactions were studied and highest affinity was reported for GCT ID, 343129 (-9.09 Kcal/mol), 341772 (-8.90 Kcal/mol) and 268776 (-8.85 Kcal/mol). These compounds were analysed for their drug like properties and toxicity which projected acceptable blood brain barrier permeation and human intestinal absorption and reduced lipotoxicity. Thus the results suggest further synthesis of new thipyridine series of compounds and experimental testing against drug resistant Staphylococcal infections

KEYWORDS: ADMET analysis; ENR inhibition; Molecular dynamics; Molecular Docking; 2D-QSAR; Thiopyridine Series

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