Synthesis, molecular modeling investigation, molecular dynamic and ADME prediction of some novel Mannich bases derived from 1,2,4-triazole, and assessment of their anticancer activity

Abstract

A series of biologically active novel Mannich bases containing with a 1<i>H</i>-1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, the synthesized Schiff Bases (<b>S1-5</b>) were reacted with formaldehyde and morpholine, which is a secondary amine to yield novel <i>N</i>-Mannich bases (<b>M1-5</b>) <i>via</i> the Mannich reaction. The structures of the compounds (<b>M1-5</b>) were determined structurally employing ¹H/¹³C-NMR, IR and elemental analysis. In this study, we evaluated the cytotoxic potential of the compounds (<b>M1-5</b>) on the human hypopharyngeal carcinoma FaDu cells. We found that the compound (<b>M3</b>) possesses a significant anticancer feature against FaDu cells that might be evaluated with further <i>in vitro</i> and <i>in vivo</i> studies to understand its anticancer potential better. Lastly, comparisons were made using molecular docking calculations to find the theoretical activities of the compounds (<b>M1-5</b>). The docking score parameter of the compound (<b>M3</b>) against the 2DO4 protein is -5.67, the docking score parameter against the 5JPZ protein is -5.72, and finally, the docking score parameter against the 2H80 protein is -5.50. Molecular dynamic calculations are made for 0-100 ns. The ADME/T calculations were performed to find the drug potential of the compounds (<b>M1-5</b>). The results suggest that our drug candidate compound exhibits strong potential for co-administration with the antigen structures, owing to the low rate of interactions that decreased over time.Communicated by Ramaswamy H. Sarma.