Synthesis and Biological Evaluation of Seco-Coumarin/Furoxan Hybrids as Potent Anti-Tumor Agents to Overcome Multidrug Resistance via Multiple Mechanisms.

ABSTRACT: In this study, twenty-four new furoxan and seco-coumarin hybrids were synthesized, and their antiproliferative activities against four breast cancer cells (MCF-7/ADR, MCF-7, MDA-MB-231, and MDA-MB-468) were evaluated. Among them, compound 9e exhibited significant toxicity against MCF-7/ADR cells compared to MCF-7 cells, with a 1401-fold increase, indicating its high collateral sensitivity. Meanwhile, 9e exhibited relatively lower toxicity to normal cell lines and improved solubility compared to the previous active compound, 4A93, which features a coumarin integrity core. Preliminary pharmacological studies revealed that 9e might be a potential P-glycoprotein substrate, which enters the lysosomes of MCF-7/ADR to release effective concentrations of nitric oxide, p

SUBMITTER: Qu F 

PROVIDER: S-EPMC12156367 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature