New hybrid compounds belonging to the class of 1,4-disubstituted 1,2,3-triazoles were synthesized. The structural characterization of the synthesized compounds was performed using IR, 1H-NMR, 13C NMR and elemental analysis techniques. Diarylketones 1a and 1b were used as starting compounds for the synthesis of triazoles. The corresponding diarylmethanol derivatives (2a,b) were obtained from reduction of ketone units with NaBH4. Oxyalkynes (3a,b) were obtained by treating the hydroxyl group with NaH in anhydrous THF and then with propargylbromide. The target hybrid structures 6a-n were obtained from the metal-catalyzed "click reaction" of the arylazide and alkyne units. The newly synthesized compounds were structurally analysed using 1H-NMR, 13C-NMR, elemental analysis, LC-MS and FT-IR. The antioxidant and anticancer activities of all compounds were investigated. It has been determined that the new hybrid structures have very good antioxidant and anticancer activities according to the standards. In particular, compounds 6b, 6h, 6i and 6j (IC50: 1.87, 12.5, 7.22, 8.04 µM) showed excellent activity compared to standard 5-Fu (IC50: 40.89 µM). According to the results of molecular docking of compounds 6b and 6i with the highest cancer activity, MetAP-2 was found to have a high affinity through exposed polar and apolar contacts with fundemental residues in the binding pocket.Communicated by Ramaswamy H. Sarma.
Keywords: 1.2.3-triazole; Diarylmethanol; antioxidant activity; click chemistry; hybrid drug; molecular docking; prostate cancer.