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1.
Chem Biodivers ; 10(3): 442-51, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23495160

ABSTRACT

Patients diagnosed with Alzheimer's disease (AD) show a characteristic neurochemical deficit of acetylcholine, especially in the basal forebrains. The use of acetylcholinesterase (AChE) inhibitors to retard the hydrolysis of acetylcholine has been suggested as a promising strategy for AD treatment. In this study, we evaluated the acetylcholinesterase inhibitory (AChEI) activities of 134 extracts obtained from 45 species of marine sponges. Thin-layer chromatography (TLC) and microplate assays reveal potent acetylcholinsterase inhibitory activities of two AcOEt extracts from the sponges Pericharax heteroraphis and Amphimedon navalis PULITZER-FINALI. We further investigated the inhibitory kinetics of the extracts and found them to display mixed competitive/noncompetitive inhibition and associated their inhibitory activity partly to terpenoids. Acetylcholinesterase inhibitors from marine organisms have been rarely studied, and this study demonstrated the potential of marine sponges as a source of pharmaceutical leads against neurodegenerative diseases.


Subject(s)
Acetylcholinesterase/chemistry , Cholinesterase Inhibitors/chemistry , Porifera/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Animals , Cholinesterase Inhibitors/metabolism , Cholinesterase Inhibitors/therapeutic use , Chromatography, Thin Layer , Humans , Kinetics , Mauritius , Protein Binding
2.
Environ Toxicol Pharmacol ; 34(2): 397-408, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22743579

ABSTRACT

The ocean is an exceptional source of natural products with many of them exhibiting novel structural features and bioactivity. As one of the most interesting phylum with respect to pharmacological active marine compounds, Poriferas have been investigated widely in the last few decades. A total of 60 organic extracts (hexane, ethyl acetate and butanol) from 20 species of marine sponges from Mauritius were screened at 50µg/ml in an in vitro screening assay against 9 human cancer cell lines. From these tested extracts, many exhibited pronounced cytotoxic effect at least in one of the cell lines and cell type cytotoxic specificity was observed. 27% of ethyl acetate, 11% of hexane and 2% of butanol extracts were found to possess a cytotoxicity ≥75% on 9 different cancer cell lines with the sponges Petrosia sp. 1, Petrosia sp. 2, Pericharax heteroraphis and Jaspis sp. being the most active. Overall, the HL-60cells were much more sensitive to most of the extracts than the other cell lines. We further evaluated the properties of the ethyl acetate (JDE) and hexane extract (JDH) of one sponge, Jaspis sp. on KB cells. JDE displayed a smaller IC(50) than JDH. Clonogenic assay confirmed the antiproliferative effect of both extracts while mitochondrial membrane potential change and microscopic analysis demonstrated extracts-induced apoptosis. Treatment with 100ng/ml of JDE led to a significant increase of cells (24h: 4.02%; 48h: 26.23%) in sub-G1 phase. The cytotoxic properties of the tested extracts from these sponges suggest the presence of compounds with pharmacological potential and are currently undergoing fractionation to isolate the active constituents.


Subject(s)
Antineoplastic Agents/pharmacology , Biological Products/pharmacology , Complex Mixtures/pharmacology , Porifera , 1-Butanol/chemistry , Acetates/chemistry , Animals , Apoptosis/drug effects , Cell Cycle/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Hexanes/chemistry , Humans , Inhibitory Concentration 50 , Mauritius , Membrane Potential, Mitochondrial/drug effects , Solvents/chemistry
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