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.

A series of biologically active novel Mannich bases containing with a 1 H -1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, the synthesized Schiff Bases ( S1-5 ) were reacted with formaldehyde and morpholine, which is a secondary amine to yield novel N -Mannich bases ( M1-5 ) via the Mannich reaction. The structures of the compounds ( M1-5 ) were determined structurally employing ¹ H/ ¹³ C-NMR, IR and elemental analysis. In this study, we evaluated the cytotoxic potential of the compounds ( M1-5 ) on the human hypopharyngeal carcinoma FaDu cells. We found that the compound ( M3 ) possesses a significant anticancer feature against FaDu cells that might be evaluated with further in vitro and in vivo studies to understand its anticancer potential better. Lastly, comparisons were made using molecular docking calculations to find the theoretical activities of the compounds ( M1-5 ). The docking score parameter of the compound ( M3 ) 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 ( M1-5 ). 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.