Cytotoxicity of Sesquiterpenes Ferulenol and Coladin on Liver FAO and B16F1 Melanoma Cells

Background: Ferula vesceritensis is an indigenous plant of Algerian Sahara riche in sesquiterpene coumarins. Objective: In this study, we investigated the biological activity of sesquiterpene coumarins; coladin, ferulenol, and lapiferin (10_‑acetoxy‑6_‑angeloyloxy‑8_,9_‑epoxy‑trans‑caxotan‑4_‑ol) isolated for the first time from the crude extract CH2Cl2–MeOH (1:1) of the roots of F. vesceritensis Coss. et Dur. Materials and Methods: Structures of coladin, ferulenol, and lapiferin were determined by extensive nuclear magnetic resonance (NMR) analyses, including 1D‑(1H and 13C) and 2D‑NMR experiments (correlation spectroscopy, heteronuclear single‑quantum coherence, heteronuclear multiple bond correlation (HMBC), and nuclear overhauser effect spectroscopy) as well as high‑resolution electron ionization mass spectra and mass spectroscopy analyses. Results: Tested on mouse B16F1 melanoma cells, ferulenol, coladin, and lapiferin exhibited a significant decrease in cell proliferation and a decrease of mitochondrial dehydrogenase activity evaluated on living FAO cells and B16F1 melanoma cells with the WST‑1 throughout an apoptotic pathway. They displayed pro‑apoptotic effects observed by a decrease in mitochondrial membrane potential and the mitochondrial respiratory rate on isolated liver mitochondria in a dose‑dependent manner. Conclusion: Our results highlight the importance of the sesquiterpene coumarins extracted from F. vesceritensis as new biologically active natural products against cancer cells.