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 (3). 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.
Marie Guillaume - IRD
Translation : Nicholas Flay
(1) The IRD, the CNRS and Pierre Fabre Laboratories are working together in research on new natural compounds with pharmacological potential. The research project on tropical antimalarial compounds, by rapid screening of the flora and flora, financed by the research programme Pal+, extends this partnership to INSERM and universities from industrialized countries and countries of the South.
(2) E. Kourany-Lefoll, C. Debitus et al., 1992 - Phloeodictines A and B : New Antibacterial and cytotoxic Bicyclic Amidinium Salts from the New Caledonian Sponge, Phloeodictyon sp., The Journal of Organic Chemistry 57, 3832-3835.
E. Kourany-Lefoll, C. Debitus et al., 1994 - Phloeodictines A1-A7 and C1-C2, Antibiotic and Cytotoxic Guanidine Alkaloids from the New Caledonian Sponge, Phloeodictyon sp. Tetrahedron 50 3415-3426.
(3) The phloeodictines have a side chain ending in a guanidine group and a carbon chain of variable length. Types B and C carry a supplementary thioethylguanidine side chain.
FOR FURTHER INFORMATION
Cécile Debitus - UMR 152 " Pharmacochimie des substances naturelles et pharmacophores redox " IRD-UPS. Institut de Sciences et Technologies du Médicament de Toulouse, 3 rue des satellites, 31400 Toulouse, France, Tel. 33-534-321-408; Fax. 33-534-321-414 Email : firstname.lastname@example.org
or Michel Sauvain - UR 152 " Pharmacochimie des substances naturelles et pharmacophores redox " IRD-UPS. Faculté des Sciences Pharmaceutiques, 35 chemin des Maraîchers, 31062 Toulouse cedex 4, France. Tel.: 33-562-256-886, Fax: 33-562-256-852. Email : email@example.com