Cytotoxic furanosesquiterpenoids and steroids from Ircinia mutans sponges.

CONTEXT: Ircinia mutans Wilson (Irciniidae) is a sponge with antimicrobial and cytotoxic constituents. OBJECTIVE: Our objective was to characterise the cytotoxic constituents of two seasonal collections of I. mutans. MATERIALS AND METHODS: The sponges were extracted in methanol-dichloromethane and their constituents were purified and characterised using column chromatography, GC-MS, 1 D and 2 D NMR. Anti-proliferative activities of the compounds, were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (0.25-100 µg/mL, 72 h) against leukaemia (MOLT-4), breast (MCF-7) and colon cancer (HT-29) human cells. RESULTS: Three furanosesquiterpoids; furodysin (1), ent-furodysinin (2) and furoircin (3) and ten sterols were characterised in I. mutans, for the first time. Cholesterol (4), cholesta-5, 7-dien-3ß-ol (5) and ergosterol (6) were determined in the sponge from the winter collections, while cholesta-5, 22-dien-3ß-ol (7), 24-methyldesmosterol (8), campesterol (9), stigmasterol (10), γ-ergostenol (11), chondrillasterol (12) and γ-sitosterol (13) were detected in the summer samples. The steroids from the winter collection exhibited cytotoxic activity with IC50 values of 13.0 ± 0.9, 11.1 ± 1.7 and 1.1 ± 0.4 µg/mL, against the mentioned cancer cell lines, respectively, while those from the summer sample, showed greater activity, IC50 = 1.1 ± 0.2 µg/mL against MOLT-4. The purified steroids showed potent MOLT-4 cytotoxic activity, IC50 values = 2.3-7.8 µg/mL. DISCUSSION AND CONCLUSION: The present study suggests that I. mutans is a rich source of cytotoxic steroids, and introduces 3 as new natural product. Considering the high cytotoxic activity of the steroids, these structures could be candidates for anticancer drug development in future research.

In vitro anti-proliferative activities of the sterols and fatty acids isolated from the Persian Gulf sponge; Axinella sinoxea.

PURPOSE: Marine sponges are rich sources of anticancer metabolites. Axinella sinoxea is a less studied sponge, found in the Larak Island's waters, of the Persian Gulf. In the present study, we have explored the cytotoxic properties and chemical constituents of A. sinoxea. METHODS: Repeated silica gel flash column chromatography of methanol extract of the Axinella sinoxea sponge, yielded fatty acid and sterol fractions. These fractions were analyzed by GC-MS and their anti-proliferative activities were evaluated by MTT assay against three human cancer cell lines including MOLT-4, MCF-7 and HT-29 as well as NIH/3 T3 fibroblast cells. The sterol-rich fractions were pooled and purified by HPLC and its sub fractions' cytotoxic activities were evaluated by MTT assay against MOLT-4 and NIH/3 T3 cells. RESULTS: The GC-MS spectral analysis of a fraction eluted with hexane: diethyl ether (90: 10), resulted in the identification of twelve fatty acids, including five linear chain saturated fatty acids; tetrdecanoic acid (1), pentadecanoic acid (3), hexadecanoic acid (5), heptadecanoic acid (7), and octadecanoic acid (10); one branched chain isoprenoid fatty acid, 4,8,12-trimethyltridecanoic acid (2); four monoenoic fatty acids; 9-hexadecenoic acid (4), 7-methyl-6-hexadecanoic acid (6), 9-octadecenoic acid (8) and 11-octadecenoic acid (9) and two polyunsaturated fatty acids; 5,8,11,14-eicosatetraenoic acid (11) and 4,7,10,13,16,19-docosahexaenoic acid (12). Spectral analysis of a non-polar fraction eluted with hexane: diethyl ether (85: 15), resulted in the identification of eight steroids including: cholesta-5,22-dien-3ß-ol (13), cholest-5-en-3ß-ol (14), ergosta-5,22-dien-3ß-ol (15), ergost-5-en-3ß-ol (16), stigmasta-5,22-dien-3ß-ol (17), γ-sitosterol (18), 33-norgorgosta-5,24(28)-dien-3ß-ol (19) and stigmasta-5,24(28)-dien-3ß-ol (20). Fatty acids-containing fraction was active against HT-29 cell line with IC50 26.52 ± 8.19 µg/mL, while the steroids-rich fraction was active against the three above mentioned cell lines with IC50 values of 1.20 ± 0.24, 4.12 ± 0.40 and 2.47 ± 0.31 µg/mL, respectively. All of the above-mentioned fractions and sub-fractions were inactive (IC50s > 50 µg/mL) when assayed against normal fibroblast cells. CONCLUSION: The present study suggests A. sinoxea as a potential natural source of cancer chemotherapeutics. Graphical abstract Cytotxic constituents of Axinella sinoxea.