Computational Designing and Prediction of ADMET Properties of Four Novel Imidazole-based Drug Candidates Inhibiting Heme Oxygenase-1 Causing Cancers.

The overexpression of heme oxygenase-1 (HO-1) contributes to the development of several types of cancers. The inhibition of HO-1 through imidazole-based drugs, which is non-competitive with heme, is a focus of anticancer drug research. We designed the four following novel HO-1 inhibiting compounds: 2-(1-cyclopentyl-4-(1H-imidazol-4-yl)butan-2-yl)pyrazine (M11), 2-[(2-chloro-3-methylcyclohexyl)methyl]-1H-imidazole (M26), 2-(2-phenethyl-1H-imidazol-4-yl)ethanesulfonamide (M28), and 5-chloro-2-[2-(2,5-dihydro-1H-imidazol-2-yl)propan-2-yl]-1H-imidazole (M31). All compounds showed a strong binding affinity with HO-1 in molecular docking studies. The in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) data showed that the compounds would be available orally in an acceptable manner. The bioactivity scores revealed that they were moderately active substances. They were found as non-mutagen, non-tumorigenic, non-irritant, and non-detrimental to the reproductive system. Finally, the drug-likeness values of the compounds were obtained as -0.71, -1.64, -2.04, and 0.4 respectively, with the final drug-score of 0.60, 0.54, 0.51, and 0.77 respectively.