Synthesis and molecular docking analysis of MBH adducts' derived amides as potential β-lactamase inhibitors

• Published in: Bioinformation Vol. 20; no. 5; pp. 449 - 459
• Main Authors: Ullah, Hamid, Majid, Sadia, Abro, Asma, Rahman, Taj Ur, Khan, Abdul Majeed, Ahmed, Mehboob, Asif, Muhammad, Yousafzai, Asma, Ullh, Riffat, Pushparaj, Peter Natesan, Rasool, Mahmood
• Format: Journal Article
• Language: English
• Published: Singapore Biomedical Informatics 31-05-2024
• Subjects: Adducts; Aldehydes; Ambient temperature; Amides; Antibacterial agents; Antibiotics; Antiinfectives and antibacterials; Chemical synthesis; Drug metabolism; Inhibitors; Lewis base; Magnetic resonance spectroscopy; Mass spectrometry; Mass spectroscopy; Molecular docking; NMR spectroscopy; β Lactamase; β-lactamase inhibitors; Synthesis; ADME properties; antibacterial amides; in silico studies; MBH adducts
• ISSN: 0973-2063; 0973-8894; 0973-2063
• DOI: 10.6026/973206300200449

Humans suffer from various diseases that require more specific drugs to target them. Among the different potent agents,
s serve as good antibacterial agents; however,
s are resistant to such antibiotics. The present study was designed to prepare efficient
inhibitor amides (12-15) from inexpensive, easily accessible, and bioactive precursors; Morita Baylis Hillman (MBH) adducts (5-8). The adducts (5-8) were primarily prepared by treating their respective aldehydes with the corresponding acrylate in the presence of an organic Lewis base at ambient temperature. The compounds were characterized using mass spectrometry, FTIR and NMR spectroscopy. Furthermore,
studies (using AutoDock Tools and AutoDock Vina programs) on the adduct and corresponding amide product revealed that all MBH adducts (5-8) and their product amides (12-15) are significant inhibitors of
. Additionally, among the MBH adducts, adduct 7 showed the highest binding affinity with
, whereas amide 15 was identified as a highly potent antibacterial based on its docking score (-8.6). In addition, the absorption, distribution, metabolism, and excretion (ADME) test of the synthesized compounds demonstrated that all compounds showed drug-likeness properties.