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

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.