DESIGNING, SYNTHESIS AND BIOLOGICAL EVALUATION OF PYRAZOLINE DERIVATIVES TARGETING PANCREATIC CANCER CELLS

Abstract

In continuation of the previous work based upon pyrazoline derivatives having cytotoxic activity, twenty-one 1,3,5-substituted pyrazoline derivatives were designed taking into consideration the important functional groups of methisazone, sorafenib and chalcone. the designed derivatives were screened using a preliminary molecular docking simulation study for evaluation of their binding interactions with receptor-2 of vascular endothelial growth factor, i.e., pDb ID: 3WZD. the synthesized derivatives were biologically evaluated for in vivo anti-angiogenic activity using adult zebrafish, its embryo, and in vitro anti-proliferative activity against pancreatic cancer mIA-pA-CA-2 cell line using the sulforhodamine b assay. Compound 5b emerged as a promising hit molecule as it manifested moderate in vitro cytotoxic activity. besides, its ability to inhibit zebrafish caudal fin regeneration with less phenotypical changes in zebrafish embryos suggests its promising potential against pancreatic cancer by VeGFR-2 inhibition as a mode of action.