Synthesis, anticancer, antioxidant activities and in silico studies of novel benzhydrylpiperazine bearing Δ 2 -1,2,3-triazoline hydrides

Abstract

Abstract To investigate the antiproliferative activity associated with the piperazine framework, a series of benzhydryl piperazine derivatives 8–18 were synthesized and characterized both spectroscopically and structurally. The antiproliferative activity of these compounds against eight human tumor cell lines was assessed. Among the tested compounds, compound 11 exhibited the highest potency, effectively inhibiting the proliferation of three selected human cancer cell lines, HL-60, Z138, and DND-41 with IC50 values of 16.80, 18.50 and 19.20 µM, respectively. Compound 10 displayed IC50 values of 19.90, 18.00 and 18.50 µM against the cell lines HL-60, Z138 and DND-41, whereas compound 13 showed IC50 value of 19.90 µM against cell line DND-41. However, all compounds exhibited IC50 values ranging from 22.95 and 58.45 µM against other tested cancer cell lines. These finding suggest that derivative 11 would be a promising potential lead compound for the development of novel antiproliferative agents. Further compounds 8–18 were evaluated for their antioxidant activity. Additionally, predictive docking studies were performed on the three-dimensional structures of acute myeloid leukemia (CDK2/cyclin A2, PDB: 7B7S, and protein kinase Akt1 PKB alpha, PDB: 4GV1).