Torres, Y.R., Berlinck, R.G.S., Magalhães, A., Schefer, A.B., Ferreira, A.G., Hajdu, E. and Muricy, G., “Arenosclerins A – C and Haliclonacyclamine E, New Tetracyclic Alkaloids from a Brazilian Endemic Haplosclerid Sponge Arenosclera brasiliensis”, Journal of Natural Products, 63, 1098-1105 (2000).

Abstract: Arenosclerins A (2), B (3) and C (4), as well as haliclonacyclamine E (1), are new tetracyclic alkylpiperidine alkaloids which have been isolated from a new species of marine sponge belonging to the Order Haplosclerida, Arenosclera brasiliensis, a species endemic to the Southeastern Brazilian coast. The alkaloids were isolated as their hydrochloride salts, and identified by analysis of spectroscopic data. Data obtained from 1H-1H COSY, HMBC and HSQC-TOCSY NMR experiments allowed complete assignment of the 1H and 13C resonances, and analysis of the NOESY and ROESY spectra showed that the only differences between 2, 3 and 4 were the relative stereochemistries of the bis-piperidine ring system. Arenosclerins A – C are the first haliclonacyclamine/halicyclamine related alkaloids with a hydroxy group in the bridging alkyl chain.

Nascimento, G.G.F., Torres, Y.R., Berlinck, R.G.S., Activity of Marine Sponges Extracts on Antibiotic Resistant Bacteria, European Journal of Pharmaceutical Sciences, 2001, 1001, S115.

Torres, Y. R., Berlinck, R. G. S., Nascimento, G.G.F., Fortier, S.C., Pessoa, C., Moraes, M.O., Antibacterial activity against resistant bacteria and cytotoxicity of four alkaloid toxins isolated from the marine sponge Arenosclera brasiliensis”, Toxicon, 40, 885-891 (2002).

Arenosclerins A – C and haliclonacyclamine E, new tetracyclic alkylpiperidine alkaloids isolated from the marine sponge Arenosclera brasiliensis, were subjected to antimicrobial and cytotoxic bioassays. Fourteen samples of microorganisms were used: Candida albicans, Staphylococcus aureus, Escherichia coli, and twelve antibiotic-resistant bacteria isolated from hospital environment. The minimum inhibitory concentration activity of each alkaloid was determined. The four compounds displayed antibacterial activity, but no antifungal activity against C. albicans. Haliclonacyclamine E and arenosclerins A and C were active against a largest number of bacteria strains than arenosclerin B. However, arenosclerins B and C presented more potent antibacterial activity. The alkaloids displayed inhibitory activity against both Gram positive and Gram negative bacteria. Cytotoxicity bioassays using the MTT method showed that these compounds present cytotoxic activity against human HL-60 (leukemia), L929 (fibrosarcoma), B16 (melanoma) and U138 (colon) cancer cell lines, at concentrations between 1.5 and 7.0 mg/mL. The results obtained indicated that A. brasiliensis alkaloids have a potent toxic activity. The broad cytotoxic and antimicrobial activities presented by A. brasiliensis alkaloids suggest a defensive role of arenosclerins and haliclonacyclamine E against microbial infection and/or the action of potential predators at the sponge’s natural habitat.