AbstractHerein, a novel series of 1,5âdisubstitutedâ1,2,3âtriazolines containing 1â(4âchlorobenzhydryl) piperazine moiety (8â18) were synthesised and evaluated for their anticancer activity across eight human tumor cell lines. Remarkably, compound 11 substituted with 3âacetylphenyl group was the most potent anticancer agent against three selected human cancer cell lines (HLâ60, Z138, and DNDâ41) with IC50 values of 16.80, 18.50, and 19.20 ÎŒM, respectively. In contrast, analogue 10 demonstrated activity against HLâ60, Z138, and DNDâ41 cell lines, with IC50 values of 19.90, 18.00, and 18.50 ÎŒM, respectively. Moreover, derivative 13 substituted with 4âbromophenyl moiety displayed activity with IC50=19.90 ÎŒM against the DNDâ41 cell line. However, all analogues showed IC50 values ranging from 22.95 to 58.45 ÎŒM when tested against other investigated cancer cell lines. These findings suggest that derivative 11 holds promise as a potential candidate for synthesizing novel anticancer agents. Furthermore, compounds 8â18 were screened for their antioxidant activity. Molecular docking studies of compound 11 on crystal structures of two proteins, CDK2/cyclin A2 (PDB: 7B7S) and kinase Akt1 PKB alpha (PDB: 4GV1) have been studied.