Design, Synthesis, and Antiproliferative Evaluation of Piperine Derivatives

Abstract –The parent nuclear structure of piperine served as the basis for the design and synthesis of thirteen derivatives through nucleophilic substitution method. These derivatives were subsequently characterized by 1H NMR, 13C NMR, and HR-MS analysis. The antiproliferative activities of these compounds against 293T human normal cells, as well as MDA-MB-231 (breast) and Hela (cervical) cancer cell lines were assessed through the MTT assay. Compound 4b exhibited remarkable antiproliferative activity against Hela cells (IC50 = 1.80 μM), surpassing that of both 5-fluorouracil (IC50 = 44.58 μM) and piperine itself. Furthermore, subsequent investigations revealed that compound 4b displayed significant anti-proliferation, anti-migration and anti-invasion effects on Hela cells. These findings suggest that compound 4b may be a promising lead compound for the treatment of cervical carcinoma.