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Vol. 37 No. 5 (2025): Vol 37 Issue 5, 2025

Copyright (c) 2025 Simplice KOUDJINA, John A. Agwupuye, Terkumbur E. Gber, Muhammad Zeeshan, Providence B. Ashishie, Sidra Batool, Prince David, Eleonore Y. Ladekan, Guy Y.S. Atohoun

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Mechanistic Molecular Insights and Quantum Biological Properties of Methyl-Imidazole Derivatives as Potential Anticancer Agents

https://doi.org/10.14233/ajchem.2025.33290
Simplice Koudjina
National High School of Applied Biosciences and Biotechnologies (ENSBBA), National University of Sciences, Technology, Engineering and Mathematics (UNSTIM), BP 486 Abomey, Sogbo-Aliho, Benin; Laboratory of Chemical Physics-Materials and Molecular Modeling, University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou, Benin
https://orcid.org/0000-0003-3029-6458
John A. Agwupuye
Department of Pure and Applied Chemistry, Faculty of Physical Sciences, University of Calabar, Calabar, Nigeria
https://orcid.org/0000-0002-1798-1058
Terkumbur E. Gber
Department of Pure and Applied Chemistry, Faculty of Physical Sciences, University of Calabar, Calabar, Nigeria
https://orcid.org/0000-0002-1901-3675
Muhammad Zeeshan
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, Henan, China
https://orcid.org/0000-0001-6615-4756
Providence B. Ashishie
Department of Pure and Applied Chemistry, Faculty of Physical Sciences, University of Calabar, Calabar, Nigeria
https://orcid.org/0000-0002-3473-290X
Sidra Batool
Department of Chemistry, University of Okara, Okara-56300, Pakistan
https://orcid.org/0009-0006-0505-9038
Prince David
Department of Pure and Applied Chemistry, Faculty of Physical Sciences, University of Calabar, Calabar, Nigeria
Eleonore Y. Ladekan
Laboratory of Physical Organic Chemistry and Synthesis, University of Abomey-Calavi (UAC), 02 BP 69 Bohicon, Benin
Guy Y.S. Atohoun
Laboratory of Chemical Physics-Materials and Molecular Modeling, University of Abomey-Calavi (UAC), 03 BP 3409 Cotonou, Benin

Corresponding Author(s) : Simplice Koudjina

simplice.koudjina@unstim.bj

Asian Journal of Chemistry, Vol. 37 No. 5 (2025): Vol 37 Issue 5, 2025

Abstract

Methyl-imidazole derivatives are attracting considerable scientific attention because of their extensive and significant bioactivities. Hence, this work focuses on the investigation of the geometry, frontier molecular orbitals (FMOs), HOMO-LUMO energy gap, molecular docking, bioavailability, ADMET and pharmacokinetic properties of 1-(4-methoxyphenyl)-2,4,5-trimethyl-1H-imidazole (M1), 4-(4,5-dimethyl-1H-imidazol-1-yl)benzenesulfonic acid (M2), N-hydroxy-N-(4-(2,4,6-trimethyl-1H-imidazol-1-yl)phenyl)hydroxylamine (M3) and 2,4,5-trimethyl-1H-imidazole (M4) respectively, utilizing DFT at 6-311++g(d,p) basis set with different functionals viz. B3LYP, B3PW91, M062X, PBE0 and ωB967XD. A high-level quantum computational study and molecular docking were performed to ascertain the stability, reactivity and drug likeness of the titled molecules. Especially, compound M2 had the least energy gap (3.92 eV) and its reactivity can be explained based on the attached sulphonic substituent compared to M1, M3 and M4, respectively. Interestingly, the studied compounds showed good biological activities against various cancer proteins with PDB IDs 3F66, 4XVE, 1XF0 and 5Y8Y. The studied molecules present a valuable opportunity for developing cancer drugs with improved therapeutic indices.

Keywords

Methyl-imidazole derivatives ADMET Molecular docking DFT
(1)
Koudjina, S.; Agwupuye, J. A.; Gber, T. E.; Zeeshan, M.; Ashishie, P. B.; Batool, S.; David, P.; Ladekan, E. Y.; Atohoun, G. Y. Mechanistic Molecular Insights and Quantum Biological Properties of Methyl-Imidazole Derivatives As Potential Anticancer Agents. ajc 2025, 37, 1211-1223.
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