Resveratrol/Hydrazone Hybrids: Synthesis and Chemopreventive Activity against Colorectal Cancer Cells

Abstract

A series of resveratrol/hydrazone hybrids were obtained and elucidated by spectroscopic analysis. All compounds were evaluated against colorectal cancer cells (SW480 and Sw620) and nonmalignant cell lines (HaCaT and CHO-K1) to establish the selectivity index. Among the hybrids evaluated, compounds 6e and 7 displayed the highest cytotoxic activity with IC50 values of = 6.5 ± 1.9 µM and 19.0 ± 1.4 µM, respectively, on SW480 cells. In addition, hybrid 7 also exhibited activity on SW620 cells with an IC50 value of 38.41 ± 3.3 µM. Both compounds were even more toxic against these malignant cells in comparison to the nonmalignant ones, as evidenced by higher selectivity indices 48 h after treatment. These compounds displayed better activity and selectivity than parental compounds (PIH and Resveratrol) and the reference drug (5-FU). In addition, it was observed that both compounds caused antiproliferative activity probably exerted by cell cycle arrest at the G2/M or G0/G1 phases, with the formation of cells in the subG0/G1 phase. Furthermore, it was noticed that compound 7 induced mitochondrial depolarization in SW480 cells and positive staining for propidium iodide in both cancer cell lines, suggesting cell membrane damage involving either apoptosis or other processes of death.

Resveratrol triggers autophagy‐related apoptosis to inhibit the progression of colorectal cancer via inhibition of FOXQ1

“…In particular, monomeric compounds from traditional Chinese medicine, extracted from natural botanical sources, are widely recognised for their potential in adjunctive therapy against malignant tumours (Bilgin et al, 2023; Esmeeta et al, 2022; Li et al, 2008). Monomeric compounds demonstrate anticancer effects in CRC by inducing ferroptosis (Brockmueller, Girisa, Motallebi, et al, 2023; Zhang et al, 2022), apoptosis (Castrillon‐Lopez et al, 2022), suppression of stemness (Liao et al, 2023; Miyazaki et al, 2023) and modulation of antioxidant activities (Roshani et al, 2022; Shakibaei et al, 2015). However, the intricate molecular mechanisms that underscore their efficacy demands further in‐depth exploration.…”