The synthesis of new pyrazoline derivatives and the investigation of their biological activities

In medicinal chemistry, pyrazoline derivatives have gained great importance in anticancer drug design and development. In the present study, new pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. Among these derivatives, 1-[((5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines with IC50 values of 16.8 µM and 11.9 µM, respectively. The tumor selectivity of compound 11 was clearly seen between Jurkat human leukemic T-cell line and human peripheral blood mononuclear cells. Due to its promising anticancer activity, compound 11 was chosen for apoptosis/necrosis evaluation and DNA-cleavage analysis in U251 cells. Compound 11-treated U251 cells exhibited apoptotic phenotype at low concentration (1.5 µM). DNA-cleaving efficiency of this ligand was more significant than cisplatin and was clearly enhanced by Fe(II)-H2O2-ascorbic acid systems. This result pointed out the relationship between DNA cleavage and cell death. Key Words: Pyrazoline, oxadiazole, anticancer activity, apoptosis, DNA cleavage