New Bioactive Eudesmane-type Sesquiterpenoids From the Red Sea Soft Coral Nephthea sp

Two previously unreported eudesmane-class sesquiterpenes, (4R*,5S*,6Z,10R*)-11-hydroperoxy-8-oxo-eudesm-6-en-5α-ol (1) and (4R*,5S*,6Z,10R*)-5-acetoxy-11-methoxy-8-oxo-eudesm-6-en (2), were obtained through fractionation of the CH₂Cl₂/MeOH (1:1) extract derived from the Red Sea-derived soft coral Nephthea sp., along with three known sesquiterpenes (3-5). The structural determination of the new compounds was achieved through comprehensive analysis of spectroscopic data, including one- and two-dimensional nuclear magnetic resonance techniques and high-resolution electrospray ionisation mass spectrometry measurements. The cytotoxic activities of the newly isolated compounds (1 and 2) were evaluated using the Sulforhodamine B assay against three human carcinoma cell lines: MCF-7, HT-29 and HepG2, with doxorubicin serving as the reference drug. Metabolite 2 showed moderate cytotoxicity towards MCF-7 and HT-29 cell lines, with IC₅₀ values of 51.5 ± 2.1 and 64.1 ± 1.9 µM, respectively, and weak activity against HepG2 (IC₅₀ = 71.3 ± 2.5 µM). In contrast, compound 1 displayed weak cytotoxic effects across all tested cell lines, with IC₅₀ values of 72.8 ± 2.3 µM (MCF-7), 85.4 ± 2.7 µM (HT-29) and 95.6 ± 3.2 µM (HepG2). These findings contribute to the chemical and biological characterisation of Nephthea sp. metabolites and support further exploration of eudesmane-type sesquiterpenes as potential anticancer agents.