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DOI: 10.1055/s-0028-1084379
Anti-infective pyrroloiminoquinone alkaloids from a deep-water Alaskan sponge of the genus Latrunculia
Bioassay- and LC-MS-guided fractionation of a methanol extract from a new deep-water Alaskan sponge species of the genus Latrunculia (Class Demospongiae: Order Poecilosclerida: Family Latrunculiidae), resulted in the isolation of two new brominated pyrroloiminoquinones, discorhabdins X (3) and Y (6), along with six known pyrroloiminoquinone alkaloids, discorhabdins A (1), C (4), E (5), L (8), 3-dihydrodiscorhabdin C (2), and a benzene derivative (7). The anti-infective properties of major isolates 1, 2, and 4 were evaluated using some selected in vitro assays. Compounds 1, 2, and 4 displayed anti-HCV activity with EC50 values less than 10µM, and showed antimalarial activity against both the chloroquine-susceptible (D6) and -resistant (W2) clones of Plasmodium falciparum, with IC50 values ranging from 22 to 1300ng/ml, as well as exhibited selective antimicrobial activity against AIDS opportunistic pathogens, Methicillin Resistance Staphylococcus aureus (MRSA), Mycobacterium intracellulare, and M. tuberculosis. Although compounds 1 and 2 displayed potent and selective in vitro antiprotozoal activity, P. berghei infected mice did not respond to these metabolites due to their toxicity.
References: 1. Antunes, E.M. et al. (2005) Nat. Prod. Rep. 22:62. 2. Kobayashi, J. et al. (1987) Tetrahedron Lett. 28:4939. 3. Perry, N.B. et al. (1988) Tetrahedron 44:1727. 4. Perry, N.B. et al. (1986)J. Org. Chem. 51:5478. 5. Copp, B.R. et al. (1994)J. Org. Chem. 59:8233.