New Hybrids Based on Curcumin and Resveratrol: Synthesis, Cytotoxicity and Antiproliferative Activity against Colorectal Cancer Cells

Abstract

We synthesized twelve hybrids based on curcumin and resveratrol, and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated against SW480 human colon adenocarcinoma cells, its metastatic derivative SW620, along with the non-malignant CHO-K1 cell line. Among the tested compounds, hybrids 3e and 3i (for SW480) and 3a, 3e and 3k (for SW620) displayed the best cytotoxic activity with IC50 values ranging from 11.52 ± 2.78 to 29.33 ± 4.73 µM for both cell lines, with selectivity indices (SI) higher than 1, after 48 h of treatment. Selectivity indices were even higher than those reported for the reference drug, 5-fluorouracil (SI = 0.96), the starting compound resveratrol (SI = 0.45) and the equimolar mixture of curcumin plus resveratrol (SI = 0.77). The previous hybrids showed good antiproliferative activity.

Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol

“…This set of derivatives was evaluated against The same type of Cur-Res hybrids without the hydrazone junction were obtained more recently by Hernández et al in a study wherein they assembled the two pharmacophores of the bioactive molecules by means of cross-coupling reactions between various styrenes and a Br-substituted chalcone (obtained via Claisen-Schmidt condensation) under palladium catalysis (Figure 18). This set of derivatives was evaluated against colorectal cancer cells (SW480 and its metastatic derivative SW620), for which they exhibited IC 50 values in the micromolar range [54]. colorectal cancer cells (SW480 and its metastatic derivative SW620), for which they exhibited IC50 values in the micromolar range [54].…”

“…This set of derivatives was evaluated against colorectal cancer cells (SW480 and its metastatic derivative SW620), for which they exhibited IC 50 values in the micromolar range [54]. colorectal cancer cells (SW480 and its metastatic derivative SW620), for which they exhibited IC50 values in the micromolar range [54].…”

Proapoptotic Effect and Molecular Docking Analysis of Curcumin–Resveratrol Hybrids in Colorectal Cancer Chemoprevention

“…In previous work, we reported the synthesis of Cur/Res hybrids together with the cytotoxic and antiproliferative activities in SW480 and SW620 colon carcinoma cells. The synthesis of Cur/Res hybrids, together with the full characterization and the whole experimental processes, was previously reported by our research group [ 30 ]. Scheme 1 shows the design of the obtained hybrids [ 30 ].…”

“…The synthesis of Cur/Res hybrids, together with the full characterization and the whole experimental processes, was previously reported by our research group [ 30 ]. Scheme 1 shows the design of the obtained hybrids [ 30 ]. According to the results, hybrids 3e and 3i displayed the best activity and selectivity in SW480 cells.…”

“…We even found that hybrid molecules were more selective than the reference drug, 5-fluorouracil, the starting compound resveratrol, and the equimolar mixture of curcumin plus resveratrol. In addition, we reported good antiproliferative activity for these four hybrid molecules [ 30 ]. Considering those findings, we deepened the effect of these molecules on different mechanisms and targets and performed in silico studies of those hybrids to investigate the possible mechanism of action associated with these active molecules in colorectal cancer to identify potential candidates for further investigations in the search for potential chemopreventive agents.…”