Cytotoxicity and genotoxicity of ingenamine G isolated from the Brazilian marine sponge Pachychalina alcaloidifera.

Marine sponges belonging to the order Haplosclerida are one of the more prolific sources of new natural products possessing various biological activities. The present study examined the cytotoxic and genotoxic potential of ingenamine G, an alkaloid isolated from the Brazilian marine sponge Pachychalina alcaloidifera. Ingenamine G displayed a moderate cytotoxic activity against human proliferating lymphocytes evaluated by the MTT assay (IC(50) 15 microg/mL). The hemolytic assay showed that ingenamine G cytotoxic activity was not related to membrane disruption. The comet assay and chromosome aberration analysis were applied to determine the genotoxic and clastogenic potential of ingenamine G, respectively. Cultured human lymphocytes were treated with 5, 10, 15 and 20 microg/mL of ingenamine G during the G(1), G(1)/S, S (pulses of 1 and 6 h), and G(2) phases of the cell cycle. All tested concentrations were cytotoxic, reduced significantly the mitotic index, and were clastogenic in all phases of the cell cycle, especially in S phase. While an increase in DNA-strand breaks was observed starting with the concentration corresponding to the IC(50). The presence of genotoxicity and polyploidy during interphase and mitosis, respectively, suggests that ingenamine G at high concentrations is clastogenic and indirectly affects the construction of mitotic fuse.

Cytotoxic alkylpiperidine alkaloids from the Brazilian marine sponge Pachychalina alcaloidifera.

Four bis-piperidine alkaloids, madangamine F (1), haliclonacyclamine F (2). and arenosclerins D (3) and E (4), have been isolated from the marine sponge Pachychalina alcaloidifera and have been identified by analysis of spectroscopic data. The alkaloids displayed cytotoxic activity against different cancer cell lines. These results support the hypothesis of a common biogenetic origin for the Haplosclerida bis-piperidine and bis-pyridine alkaloids.

Ingenamine G and cyclostellettamines G-I, K, and L from the new Brazilian species of marine sponge Pachychalina sp.

The chemical investigation of the cytotoxic and antituberculosis active MeOH crude extract of the marine sponge Pachychalina sp. led to the isolation of six new nitrogenous metabolites, including ingenamine G (1), as well as a mixture of new cyclostellettamines G, H, I, K, and L (10-14) with the known cyclostellettamines A-F (4-9). Structural assignments of compound 1 were based on the analysis of MS and NMR data, while the structures of compounds 10-14 could be established by HPLC-MS/MS analysis. Ingenamine G displayed cytotoxic activity against HCT-8 (colon), B16 (leukemia), and MCF-7 (breast) cancer cell lines, antibacterial activity against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), and four oxacilin-resistant S. aureus strains, and antimycobacterial activity against Mycobacterium tuberculosis H37Rv.

Challenges and rewards of research in marine natural products chemistry in Brazil.

Brazil is blessed with a great biodiversity, which constitutes one of the most important sources of biologically active compounds, even if it has been largely underexplored. As is the case of the Amazon and Atlantic rainforests, the Brazilian marine fauna remains practically unexplored in the search for new biologically active natural products. Considering that marine organisms have been shown to be one of the most promising sources of new bioactive compounds for the treatment of different human diseases, the 8000 km of the Brazilian coastline represents a great potential for finding new pharmacologically active secondary metabolites. This review presents the status of marine natural products chemistry in Brazil, including results reported by different research groups with emphasis on the isolation, structure elucidation, and evaluation of biological activities of natural products isolated from sponges, ascidians, octocorals, and Opistobranch mollusks. A brief overview of the first Brazilian program on the isolation of marine bacteria and fungi, directed toward the production of biologically active compounds, is also discussed. The current multidisciplinary collaborative program under development at the Universidade de São Paulo proposes to establish a new paradigm toward the management of the Brazilian marine biodiversity, integrating research on the species diversity, ecology, taxonomy, and biogeography of marine invertebrates and microorganisms. This program also includes a broad screening program of Brazilian marine bioresources, to search for active compounds that may be of interest for the development of new drug leads.