2D QSAR, Design, and in Silico Analysis of Thiophene‐Tethered Lactam Derivatives as Antimicrobial Agents

Abstract

AbstractBackground: A very high rate of resistance causes health‐care‐associated and community‐acquired infections. E. coli is one of the nine pathogens of highest concern to most of the antibiotics and other class of antimicrobials. Objective: The objective of the present study is to develop novel thiophene derivatives using 2D QSAR and in silico approach for E. coli resistance. Methods: Substituted thiophene series reported by Nishu Singla et al., were taken for QSAR analysis. From the results, a set of 15 new compounds were designed. A complete in silico analysis has been done using PADEL, Autodock vina, Swiss ADME, Protox II software. Results: The designed compounds obey the Lipinski's rule of five and were known to have excellent inhibitory action (pIC50 values −0.87 to −1.46) which is similar to the most active compound of the data set (pIC50 −0.69) taken for the study. The bioavailability score (0.65) with no toxicity representing that the designed compounds are suitable for oral administration. Conclusion: The designed compounds are inactive for mutagenicity and cytotoxicity and ADMET studies states that these molecules are likely to be orally bioavailable and could be easily transported, diffused, and absorbed. So, the designed compounds will definitely serve as a lead antibacterial agent for E. coli resistance.