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.

Coronaviruses in wild birds - A potential and suitable vector for global distribution.

The recurrent appearance of novel coronaviruses (CoVs) and the mortality and morbidity caused by their outbreaks aroused a widespread response among the global science community. Wild birds' high biodiversity, perching and migratory activity, ability to travel long distances and possession of a special adaptive immune system may make them alarming sources of zoonotic CoV-spreading vectors. This review gathers the available evidence on the global spread of CoVs in wild birds to date. The major wild birds associated with different types of CoVs are Anseriformes, Charadriiformes, Columbiformes, Pelecaniformes, Galliformes, Passeriformes, Psittaciformes, Accipitriformes, Ciconiiformes, Gruiformes and so on. However, the main type of CoVs found in wild birds is gammacoronavirus, followed by deltacoronavirus. Consequently, it is imperative to enable thorough research and continuous monitoring to fill the study gap in terms of understanding their role as zoonotic vectors and the frequent appearance of novel CoVs.