New 1,2,3-triazole tethered-1,4-dihydropyridines as potential antioxidant agents: Synthesis and molecular docking study

Abstract

We have designed the molecules containing 1,2,3-triazole and 1,4-dihydropyridine pharmacophoric scaffolds in a single molecular framework by using molecular hybridization approach. Accordingly, we have planned and executed for the synthesis of a library of aryl-1,2,3-triazole incorporated 1,4-dihydropyridines and evaluated for their antioxidant activity. The compounds 12o, 12s and 12t showed excellent antioxidant activity with an IC50 values of 08.34 ± 0.17, 08.04 ± 0.17 and 08.80 ± 0.15 µg/mL, respectively. The compound 12a and 12m exhibited excellent antioxidant activity with IC50 values of 09.11 ± 0.34 and 11.39 ± 0.94 µg/mL, respectively. Furthermore, the compound 12k and 12n showed very good antioxidant activity with IC50 values of 12.22 ± 0.43 and 16.05 ± 0.11 µg/mL, respectively. In silico molecular docking study was performed to examine their binding modes and interactions with myeloperoxidase (MPO) enzyme which exhibited excellent correlation with observed antioxidant activites. Finally, in silico ADMET properties of the synthesized compounds were also investigated. The obtained results showed that most of the synthesized compounds had a positive drug-likeness profile.