Computer aided design of novel antibiotic drug candidate against multidrug resistant strains of Salmonella typhi from pyridine-substituted coumarins

Abstract

BackgroundThe rising cases of resistance to existing antibiotics by Salmonella typhi, has made the development of novel drug candidates a necessity. In this study, a data set of antibacterial pyridine substituted coumarins were subjected to Virtual Screening against SipA effector protein of the bacterium. The compounds were geometry-optimized using Semi-empirical (pm3) method in Spartan 14 software, docked against the active sites of SipA using AutoDock Vina software. The molecule with the best docked score was selected as template and subjected to structural modifications leading to the design of a novel coumarin based drug candidate codenamed Y-1.ResultsThe docking of Y-1 against SipA revealed that it binds to the target with ΔG value of − 9.1 kcal/mol. This value is better than − 6.8 kcal/mol obtained for ciprofloxacin used herein for quality assurance. Additionally, quantum mechanical calculations on Y-1 using DFT (B3LYP/6-31G* basis set) shows a wide energy gap of 3.44 eV and ω value of 1.47 eV, indicating its sound kinetic and thermodynamic stabilities. Y-1 was also found to possess good oral bioavailability and positive pharmacokinetic profiles.ConclusionThis is the first time coumarin derivatives are screened against an effector protein of Salmonella typhi. It is envisaged that the findings of this research will provide an excellent blueprint toward the development of novel antibiotics against Salmonella typhi.