Antiproliferative Isoprenoid Derivatives from the Red Sea Alcyonacean Xenia umbellata

Abstract

From the soft coral Xenia umbellata, seven isoprenoid derivatives were isolated, including a new xenicane diterpene, xeniolide O (5) and a new gorgostane derivative gorgst-3β,5α,6β,11α,20(S)-pentol-3-monoacetate (7), along with three known sesquiterpenes (1–3), a known diterpene (4), and a known steroid (6). The extensive analyses of the NMR, IR, and MS spectral data led to determination of their chemical structures. Compounds 1–7 displayed a cytotoxic effect against breast adenocarcinoma (MCF-7), hepatocellular carcinoma (HepG2), and cervix adenocarcinoma (HeLa), with IC50 values ranging between 1.5 ± 0.1–23.2 ± 1.5; 1.8 ± 0.1–30.6 ± 1.1 and 0.9 ± 0.05–12.8 ± 0.5 μg/mL, respectively. Compound 3 showed potent cytotoxic effects against MCF-7, HepG2, and HeLa with IC50 values = 2.4 ± 0.20, 3.1 ± 0.10 and 0.9 ± 0.05 μg/mL, respectively. Compounds 2, 5, and 7 displayed cytotoxic effect against Hela cells with IC50 values = 12.8 ± 0.50, 6.7 ± 1.00 and 11.5 ± 2.20 μg/mL, respectively. Two DNA binding dyes, acridine orange (AO) and ethidium bromide (EtBr) were used for the detection of viable, apoptotic, and necrotic cells. The early apoptotic cell death was observed in all types of treated cells. The late apoptotic cells were highly present in HepG2 cells. Compounds 5 and 7 induced a high percentage of necrosis towards HepG2 and HeLa cells. The late apoptosis was recorded as a high rate after treatment with 7 on all cancer cells.