Molecular Dynamics Simulation, QSAR, DFT, Molecular Docking, ADMET, and Synthesis of Ethyl 3-((5-Bromopyridin-2-yl)Imino)Butanoate Analogues as Potential Inhibitors of SARS-CoV-2

Abstract

Structural modifications of ethyl-3-((5-bromopyridin-2-yl)imino)butanoate ester enhances its biological activities. In the present work, the synthesis of a Schiff base by reacting 2-amino-5-bromo pyridine and ethyl acetoacetate was reported. Electronic properties were investigated by the computational method of density functional theory (DFT). The pass prediction score supported anti-viral efficacy which satisfied the Lipiniski rule and overall HOMO-LUMO. The most important part of this investigation was docking study which revealed that the ligands L07 has nearly efficacy to standard drugs and maximum docking score was found against Alpha variant (7EKF) at −6.7 kcal/mol, Beta variant (7ekg) at −6.2 kcal/mol, Gamma variant (7EKC) at −6.5 kcal/mol, Beta variant (7ekg) at −6.2 kcal/mol, SARS-CoV-2 Gamma variant (7EKC) at −6.2 kcal/mol, Delta variant (7V8B) at −6.1 kcal/mol and Omicron variant (7T9J) at −6.3 kcal/mol. Finally, molecular dynamics study was performed to determine the stability and it was reported that the molecules L07 has better stability to be an oral drug against the different variant of SARS-CoV-2 viral pathogen.

Keywords:

• Aminopyridine
• molecular dynamics
• QSAR
• DFT
• molecular docking
• ADMET

Acknowledgements

We are grateful to the Management and Principal of Jamal Mohamed College (Autonomous), Tiruchirappalli, Tamil Nadu, India and the common instrumentation facility center funded by DST-FIST under Star Colleges, India. We are also thankful to the Deanship of Scientific Research at King Khalid University, Saudi Arabia greatly appreciated for supporting this work under grant no: R.G.P-2/62/43.

Disclosure statement

No potential conflict of interest was disclosed by the author(s).