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



Hamid Ullah1, Sadia Majid2, Asma Abro3, Taj Ur Rahman2, Abdul Majeed Khan4, Mehboob Ahmed3, Muhammad Asif5, AsmaYousafzai3, Riffat Ullh6, Peter Natesan Pushparaj7 & Mahmood Rasool7,*



1Department of Chemistry, Balochistan University of Information Technology, Engineering and Management Sciences, Takatu Campus, Quetta 87300, Pakistan; 2Department of Chemistry, Mohi-Ud-Din Islamic University Nerian Sharif, AJ&K, Pakistan; 3Department of Biotechnology, BUITEMS, Takatu Campus, Quetta, Pakistan; 4General Studies Department, Jubail Industrial College, Jubail Industrial City 31961, Saudi Arabia; 5Department of Biotechnology & ORIC, BUITEMS, Takatu Campus, Quetta, Pakistan; 6H. E. J. Research institute of chemistry, ICCBS, University of Karachi, Pakistan; 7Center of Excellence in Genomic Medicine Research, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia; *Corresponding author



Hamid Ullah - E-mail: hamidullah9@gmail.com

Sadia Majeed - E-mail: mamchemist@gmail.com

Asma Abro - E-mail: asma.abro@buitms.edu.pk

Taj Ur Rahman - E-mail: taj_urrehman81@yahoo.co.uk

Abdul Majeed khattak - E-mail: fahmigul@yahoo.com

Mehboob Ahmed - E-mail: Mehboob.Ahmed1@buitms.edu.pk

Muhammad Asif: - E-mail: asifjallali@yahoo.com

AsmaYousafzai - E-mail: asmakhan@buitms.edu.pk

Riffat Ullah - E-mail: riffatullah20@gmail.com

Peter Natesan Pushparaj - E-mail: peter.n.pushparaj@gmail.com

Mahmood Rasool - E-mail:- E-mail: mahmoodrasool@yahoo.com


Article Type

Research Article



Received May 1, 2024; Revised May 31, 2024; Accepted May 31, 2024, Published May 31, 2024



Humans suffer from various diseases that require more specific drugs to target them. Among the different potent agents, β-lactamases serve as good antibacterial agents; however, β-lactamases are resistant to such antibiotics. The present study was designed to prepare efficient β-lactamase 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, in silico 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 β-lactamase. Additionally, among the MBH adducts, adduct 7 showed the highest binding affinity with β-lactamase, 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.



Synthesis, MBH adducts, antibacterial amides, ADME properties, in silico studies, β-lactamase inhibitors



Ullah et al. Bioinformation 20(5): 449-459 (2024)


Edited by

P Kangueane






Biomedical Informatics



This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.