Some Naringenin–Piperazine Derivatives: Synthesis, Evaluation of Synergistic Effects of Their Combination with Cisplatin

Abstract Naringenin is a natural flavonoid found in citrus fruits such as lemons or grapefruits and has biological characteristics like anti‐inflammatory, antibiotic, and anticancer. Naringenin derivatives are among the compounds that have attracted attention in recent years. We synthesized three novel compounds by a substitution reaction between naringenin and piperazine derivatives. These compounds were successfully characterized by spectroscopic analysis (FTIR, NMR, and MS). Naringenin–piperazine derivatives ( 3a , 3b , and 3c ) were explored against prostate cancer cells (DU145 and PC3 cell lines). The compound 3a showed the lowest IC 50 value. Therefore, the synergistic effect of the compound 3a + cisplatin combination was investigated. Good outcomes were attained based on dosage. Based on the outcomes of gene expression analysis and molecular probe labeling, the antiproliferative effect mechanism of compound 3a via mitochondrial apoptosis was identified.