Antimalarial activity of pyrroloiminoquinones from the Australian marine sponge Zyzzya sp.
ABSTRACT A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC(50) values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC(50) < 100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC(50) = 1-4 μM). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg(-1) day(-1).
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ABSTRACT: In the last decades researchers of natural products chemistry focused their research in a wide variety of bioactive compounds from marine species. Marine sponges (Porifera) have been ranked very high in the priority of natural product research because the discovery of a wide range of bioactive chemical components and secondary metabolites with potential pharmaceutical applications gave promising results. These discoveries have attracted the attention of pharmaceutical chemistry experts, cell biologists, chemists of natural products and medical practitioners. Since the 1950s, when a number of the first publications appeared in the scientific literature, some bioactive natural chemicals from marine sponges gave successful examples of pharmaceuticals. Initial experimental results suggest that sponges have the potential to provide future drugs against important diseases, such as cancer, a range of viral diseases, malaria, and inflammations. At the same time scientists studied the molecular mode of action of most sponge-derived metabolites and their mechanism of action were elucidated for their therapeutic potential in a variety of diseases. This review aims at describing some of the most highly cited reviews of the last decade on sponge-derived bioactive compounds and the most promising substances extracted and isolated from marine sponges for pharmaceutical applications. The review is covering mainly new developments of the last five years in the field of marine sponge metabolite research and important findings for bioactive compounds from in vitro, in vivo and clinical studies for therapeutic drug applications.Natural Products Chemistry & Research. 10/2013; 1(3).