Immune-mediated parasite clearance in mice infected with Plasmodium berghei following treatment with manzamine A.
ABSTRACT Manzamine A, a sponge-derived alkaloid, was recently shown to possess in vivo antimalarial activity against the blood stages of the rodent malaria parasite Plasmodium berghei. A single intraperitoneal dose of 100 micromol/kg of manzamine A suppressed parasite growth but was followed by parasite recrudescence. Forty percent of mice with recrudescing parasites were able to recover and clear the fulminating parasitaemia. Examination of sera from these mice revealed that infected mice treated with manzamine A had a suppressed IFN-gamma production but an increase in their IL-10 and IgG production. The prolonged survival of infected mice treated with manzamine A and the eventual clearance of recrudescing parasites in some of these mice involve a down-regulation of Thl responses and a switch to antibody dependent-Th2 responses.
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ABSTRACT: Chemical investigation of the Red Sea sponge Dragmacidon coccinea led to the isolation of a new nucleoside, dragmacidoside (1), along with eight known compounds: adenosine (2), inosine (3), deoxycytidine (4), methyl-α-d-glucopyranoside (5), clionasterol (6), stigmasterol (7), campesterol (8) and brassicasterol (9). The compounds were isolated from chloroform and ethyl acetate fractions of the methanolic extract of the sponge, and their structures were established based on various spectroscopic data including MS, 1D and 2D NMR (COSY, HSQC and HMBC). Biological testing revealed that the chloroform fraction possesses significant anti-inflammatory activity in the carrageenan-induced hind paw oedema in rats.Natural product research 05/2014; · 1.01 Impact Factor
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ABSTRACT: As part of a pilot scale project on drug discovery from local marine organisms, 19 intertidal marine organisms from Singapore waters were collected and screened for the presence of biologically-active natural products. These marine organisms were coll ected due to the ease of procurement and their rela tive abundance. The organic extracts of these organisms were prepared and screened in the brine shrimp lethality (BSL), the cytotoxicity (MCF-7 and MOLT-4 cell lines), and the quorum sensing inhibition (QS I) assays. Over 60% of the extracts gave significant biological activities in the BSL and the cytotoxici ty (MOLT-4) assays when tested at 1000 ppm. Three spo nge extracts showed moderate antibacterial activity while a fraction obtained from the gross fractionat ion of the extract of the marine cyanobacterium, Ly ngbya majuscula (PH2), exhibited anti quorum sensing acti vity in the QSI assay. Lyngbya majuscula (PH2) als o exhibited exceptional biological properties in the toxicity assays and its extract underwent further fractionation. The 1H-NMR spectra of the bioactive chromatographic frac tions derived from the microalgal extract indicated the presence of unique lipopeptid es. Data from this study provided rationale to ini tiate marine natural products research for drug discovery in Singapore.
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ABSTRACT: Manzamine A, a member of the manzamine alkaloids, was originally isolated from marine sponges of the genus Haliclona. It was recently shown to have activity against pancreatic cancer cells, but the precise mechanism of action remained unclear. To further our understanding of the mechanism of action of manzamine A, chemogenomic profiling in the yeast S. cerevisiae was performed, suggesting that manzamine A is an uncoupler of vacuolar ATPases. Fluorescence microscopy confirmed this effect on yeast vacuoles, where manzamine A produced a phenotype very similar to that of the established v-ATPase inhibitor bafilomycin A1. In pancreatic cancer cells, 10 µM manzamine A affected vacuolar ATPase activity and significantly increased the level of autophagosome marker LC3-II and p62/SQSTM1 as observed by western blot analysis. Treatment with manzamine A in combination with bafilomycin A1 (inhibitor of autophagosome-lysosome fusion) did not change the levels of LC3-II when compared to cells treated with bafilomycin A1 alone, suggesting that manzamine A is a potential inhibitor of autophagy by preventing autophagosome turnover. As autophagy is essential for pancreatic tumor growth, blocking this pathway with manzamine A suggests a promising strategy for the treatment of pancreatic cancer.Marine Drugs 01/2013; 11(9):3500-16. · 3.98 Impact Factor