Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge Scopalina ruetzleri.

OBJECTIVES: Marine sponges are among the most promising sources of chemically diversified fatty acids (FAs). In addition, several studies have shown the effect of polyunsaturated FAs on cancer therapy. This research carried out a biological and chemical evaluation of the sponge Scopalina ruetzleri collected on the South Brazilian coastline. METHODS: Bioassay-guided fractionation of S. ruetzleri was performed in human glioma (U87) and neuroblastoma (SH-SY5Y) cell lines, and the in-vitro effects on free radicals were evaluated. KEY FINDINGS: The ethyl acetate fraction of S. ruetzleri showed promising cytotoxic effects in cancer cell lines, with IC50 < 20 µg/ml. Fingerprint (1) H Nuclear Magnetic Resonance (NMR) analysis showed that this fraction is mainly constituted of FAs. Through FA methyl ester analysis, it was possible to identify 32 FAs. In addition, some minor unusual FAs for the marine biosphere were identified. The results of conjugated dienes method showed that FAs fraction, at concentrations above 50 µg/ml, has a pro-oxidant effect, indicating that lipid peroxidation may be partially responsible for the mechanism of cytotoxicity on cancer cells. CONCLUSION: This work also contributes to studies that focus on the application of FAs on cancer therapy as a new adjuvant to radio or chemotherapy, or as a chemotherapeutic agent.

Potent fluorinated agelastatin analogues for chronic lymphocytic leukemia: design, synthesis, and pharmacokinetic studies.

Chronic lymphocytic leukemia (CLL) is the most common lymphoid neoplasia in Western societies and is currently incurable. Multiple treatment options are practiced, but the available small molecule drugs suffer from dose-limiting toxicity and undesirable side effects. The need for new, less toxic treatments is a pressing concern. Here, we demonstrate that (-)-agelastatin A (1a), a pyrrole-imidazole alkaloid obtained from a marine sponge, exhibits potent in vitro activity against primary cell lines of CLL and disclose the synthesis of several analogues that are equipotent or exceed the potency of the natural product. The novel synthetic analogue, 13-debromo-13-trifluoromethyl agelastatin A (1j), showed higher activity than the natural product when tested against the same cell lines and is the most potent agelastatin derivative reported to date. A detailed in vitro structure-activity relationship of 1a in CLL compared to that of 22 synthetic analogues is described along with preliminary in vivo pharmacokinetic and metabolism studies on the most potent compounds.

Antifungal Diterpene Alkaloids from the Caribbean Sponge Agelas citrina: Unified Configurational Assignments of Agelasidines and Agelasines.

Three new diterpene alkaloids - the hypotaurocyamines, (-)-agelasidines E and F (5-6), and the adeninium salt, agelasine N (9) - were isolated from the Caribbean sponge Agelas citrina along with six known natural products agelasines B-E (7, 10-12), 2-oxo-agelasine B (8), and (-)-agelasidine C (3). The chemical structures of 5, 6 and 9 were elucidated by analysis of NMR spectra and mass spectrometry. This represents the first report of natural products from the sponge A. citrina. Unified assignment of absolute configurations of the new compounds and known compounds were achieved by chemical correlation, quantitative measurements of molar rotations, and comparative analysis by van't Hoff's principle of optical superposition. (-)-Agelasidine C (3) exhibited potent antifungal and modest cytotoxic activity against human chronic lymphocytic leukemia (CLL) cells.

Conservation of progesterone hormone function in invertebrate reproduction.

Steroids play fundamental roles regulating mammalian reproduction and development. Although sex steroids and their receptors are well characterized in vertebrates and several arthropod invertebrates, little is known about the hormones and receptors regulating reproduction in other invertebrate species. Evolutionary insights into ancient endocrine pathways can be gained by elucidating the hormones and receptors functioning in invertebrate reproduction. Using a combination of genomic analyses, receptor imaging, ligand identification, target elucidation, and exploration of function through receptor knockdown, we now show that comparable progesterone chemoreception exists in the invertebrate monogonont rotifer Brachionus manjavacas, suggesting an ancient origin of the signal transduction systems commonly associated with the development and integration of sexual behavior in mammals.

Bioactive bromophycolides R-U from the Fijian red alga Callophycus serratus.

Four new bromophycolides, R-U (1-4), were isolated from the Fijian red alga Callophycus serratus and were identified by 1D and 2D NMR and mass spectroscopic analyses. These compounds expand the known structural variety of diterpene-benzoate macrolides and exhibited modest cytotoxicity toward selected human cancer cell lines. Bromophycolide S (2) also showed submicromolar activity against the human malaria parasite Plasmodium falciparum.