New Hybrid Scaffolds Based on 5-FU/Curcumin: Synthesis, Cytotoxic, Antiproliferative and Pro-Apoptotic Effect

• Main Authors: Gustavo Moreno-Quintero (Author), Emmanuel Betancur-Zapata (Author), Angie Herrera-Ramírez (Author), Wilson Cardona-Galeano (Author)
• Format: Book
• Published: MDPI AG, 2023-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

A series of 5-FU-Curcumin hybrids were synthesized, and their structures were elucidated by spectroscopic analysis. The synthesized hybrid compounds were evaluated in different colorectal cancer cell lines (SW480 and SW620) and in non-malignant cells (HaCaT and CHO-K1), to determine their chemopreventive potential. Hybrids <b>6a</b> and <b>6d</b> presented the best IC₅₀ value against the SW480 cell line with results of 17.37 ± 1.16 µM and 2.43 ± 0.33 µM, respectively. Similarly, compounds <b>6d</b> and <b>6e</b> presented IC₅₀ results of 7.51 ± 1.47 µM and 14.52 ± 1.31 µM, respectively, against the SW620 cell line. These compounds were more cytotoxic and selective than curcumin alone, the reference drug 5-fluorouracil (5-FU), and the equimolar mixture of curcumin and 5-FU. In addition, hybrids <b>6a</b> and <b>6d</b> (in SW480) and compounds <b>6d</b> and <b>6e</b> (in SW620) induced cell cycle arrest in S-phase, and, compounds <b>6d</b> and <b>6e</b> caused a significant increase in the sub-G0/G1 phase population in both cell lines. Hybrid <b>6e</b> was also observed to induce apoptosis of SW620 cells with a respective increase in executioner caspases 3 and 7. Taken together, these results suggest that the hybrids could actively act on a colorectal cancer model, making them a privileged scaffold that could be used in future research.

Item Description

10.3390/pharmaceutics15041221
1999-4923