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

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Title	*Synthesis and molecular docking analysis of MBH adducts' derived amides as potential β-lactamase* inhibitors**
Authors	Hamid Ullah¹, Sadia Majid², Asma Abro³, Taj Ur Rahman², Abdul Majeed Khan⁴, Mehboob Ahmed³, Muhammad Asif⁵, AsmaYousafzai³, Riffat Ullh⁶, Peter Natesan Pushparaj⁷ & Mahmood Rasool^7,^*
Affiliation	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
Email	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
Date	Received May 1, 2024; Revised May 31, 2024; Accepted May 31, 2024, Published May 31, 2024
Abstract	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.
Keywords	Synthesis, MBH adducts, antibacterial amides, ADME properties, in silico studies, β-lactamase inhibitors
Citation	Ullah et al. Bioinformation 20(5): 449-459 (2024)
Edited by	P Kangueane
ISSN	0973-2063
Publisher	Biomedical Informatics
License	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.