Novel Mannich bases derived from 1,2,4-triazoles: Design, synthesis, characterization, and glutathione S-transferase inhibition properties investigations

The reaction of variously substituted 1,2,4-triazole derivatives with morpholine and formaldehyde represents an efficient and easy-to-set synthetic entry toward heterocyclic N-Mannich bases. For this purpose, the synthesized Schiff Bases (3a-g) were reacted with formaldehyde and morpholine, a secondary amine, to yield novel NMannich bases (6a-g). The structures of the compounds (6a-g) were determined structurally by employing 1H/13C-NMR, IR, and elemental analysis. The synthesized compounds were screened for in vitro biological activity, and the bioanalysis results showed that the newly synthesized compounds had different in vitro enzyme inhibition activities against Glutathione S-transferase (GST). Their Ki values were calculated in the 2.69 & PLUSMN; 0.421-21.58 & PLUSMN;6.809 & mu;M range. Besides, their IC50 values were calculated in the 1.975-2.753 & mu;M range. Also, the potential inhibitory effects of the synthesized compounds on glutathione S-transferase enzyme were evaluated by in silico method. The highest affinity values for inhibition of glutathione S-transferase enzyme were observed as 6c (-7.7 kcal/mol), 6 g (-7.4 kcal/mol), and 6b (-6.8 kcal/mol), respectively, and they gave better affinity values than standard Ethacrynic acid. Furthermore, the absorption distribution, metabolism, and excretion properties (ADME), molecular properties, toxicity estimation, and compounds' bioactivity scores were evaluated