Design, Synthesis, In-silico ADME prediction Molecular docking and Antitubercular screening of Bromo-pyridyl tethered 3-chloro 2-azetidinone Derivatives

Abstract

In the present investigation, we have designed and synthesized a new series of β-lactam derivatives 9a-j containing bromo-pyridyl moiety via [2+2]-ketenimine cycloaddition, initially the intermediate hydrazone derivatives 7a-j were synthesized via conventional and microwave methods. All the new synthesized compounds were characterized by various spectroscopic techniques (such as IR, NMR (1H, 13C), and mass spectroscopy) and elemental analysis. All the β-lactam derivatives 9a-j were subjected to in-vitro anti-mycobacterial activity against the Mycobacterium tuberculosis (H37Rv) strain via MABA methods. All the newly synthesized compounds were found to be effective in inhibiting M. tuberculosis H37Rv strain at 25.0 and 50.0 µg/mL concentrations. Among all the synthesized molecules, compound 9e exhibited potent anti-tubercular activity at 25.0 µg/mL concentration in comparison with the rest of the compounds. The In-silico ADME prediction suggests that all synthesized compounds are suitable for oral bioavailability and possess drug-like properties. In addition, molecular docking studies have been performed to gain mechanistic insight and molecular interactions against the mycobacterial InhA enzyme. The molecular dynamics simulation study was also carried out to analyze the stability of the complex docks, the conformational changes, and basic molecular interactions.

Keywords

• Antimycobacterial
• 2-azetidinone
• Molecular docking
• ADMET prediction
• Microwave