Antimalarial substances found in New Caledonian sponges

Living organisms are an enormous reservoir of natural compounds potentially active against viruses, bacteria or cancerous cells, that could lead to the development of new medicines. Out of about 145 000 natural substances described today, 10% come from marine organisms. Among the few such organisms studied for their chemical composition, sponges of the genus Phloeodictyon (Haploscleridae) collected in shallow New Caledonian waters during campaigns of the programme “Marine Substances of Biological Interest” (SMIB), have proved to contain particular organic compounds, the phloeodictines, alkaloids with powerful antibacterial properties. Up to now, only deep-water species of Phloeodictyon were thought to synthesize these alkaloids, present in all the samples of such bathyal forms taken from an array of seamounts off the southern sector of New Caledonia.

However, phloeodictines have recently been found in shallow-water Oceanapia (a taxonomic synonym of Phloeodictyon) species living on the reef off the east coast of New Caledonia, by a joint scientific team involving the IRD, the University of Trente (Italy), the CNRS and the industrial group Pierre Fabre. This discovery suggests a possible adaptation of bathyal species to the shallow-water reef environment.

The emergence of drug-resistant forms of the malarial agent Plasmodium falciparum has made essential a search for new compounds to control it. Scientists specialized in natural substances, investigating the chemical structure and properties of the phloeodictines as part of the French malaria control research programme Pal +, have revealed antimalarial activity among phloeodictines extracted from the reef sponge Oceanapia fistulosa.

The phloeodictines are a family of alkaloids, composed of three large groups distinguished according to differences in their chemical skeleton. They all carry a lateral poly-N chain and a variable-length carbon chain. Phloeodictines types B and C, which are minority compounds, carry an additional sulfurated poly-N chain. Smaller structural variations can occur in each of these three groups, in the lateral chains of variable length and degree of unsaturation, This makes for a highly complex chemical family. A combination of chromatographic and spectrometric methods obtained the characterization of 25 different compounds that belong to these three groups, extracted from Oceanapia fistulosa. Seventeen of them are new variants.

Laboratory tests involving presentation of a chloroquine-resistant strain of Plasmodium falciparum with these different components demonstrated low-dose inhibition of parasite development by type A phloeodictines, most of which were new.

A particularly promising feature of these phloeodictines’ antimalarial action is that, in vitro, it is accompanied by very low cytotoxicity. These components therefore hold potential as material for the elaboration of antimalarial medicines with new types of structure. Other investigations are planned to seek confirmation of these results and find out accurate information on this antimalarial activity in vivo, using infected rodent models, and to attempt to unravel phloeodictines’ action mechanism.

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