Alain Fournet

Antileishmanial and trypanocidal activity of Brazilian Cerrado plants

The side effects and the emerging resistance to the available drugs against leishmaniasis and trypanosomiasis led to the urgent need for new therapeutic agents against these diseases. Thirty one extracts of thirteen medicinal plants from the Brazilian Cerrado were therefore evaluated in vitro for their antiprotozoal activity against promastigotes of Leishmania donovani, and amastigotes of Trypanosoma cruzi. Among the selected plants, Casearia sylvestris var. lingua was the most active against both L. donovani and T. cruzi. Fifteen extracts were active against promastigotes of L. donovani with concentrations inhibiting 50% of parasite growth (IC50) between 0.1-10 microg/ml, particularly those of Annona crassiflora (Annonaceae), Himatanthus obovatus (Apocynaceae), Guarea kunthiana (Meliaceae), Cupania vernalis (Sapindaceae), and Serjania lethalis (Sapindaceae). With regard to amastigotes of T. cruzi, extracts of A. crassiflora, Duguetia furfuracea (Annonaceae), and C. sylvestris var. lingua were active with IC50 values between 0.3-10 microg/ml. Bioassay fractionations of the more active extracts are under progress to identify the active antiparasite compounds.

Expeditious preparation of 2-substituted quinolines

Abstract A library of 2-substituted quinolines was synthesized in solution from mixtures of Grignard reagents and a quinolinium salt. Grignard reagents were prepared in one pot, taking advantage of the entrainment method for their preparation from unreactive alkyl halides. Then mixtures of 2-alkylquinolines were readily accessible for biological tests or separated by centrifugal-partition chromatography (CPC) prior to the biological screening.

Preparative separation of quinolines by centrifugal partition chromatography with gradient elution

Centrifugal partition chromatography has been successfully applied to the separation of 2-alkylquinolines from liquid combinatorial synthesis crude samples. Original gradient elution using the ternary two-phase solvent systems heptane-water-acetonitrile and heptane-acetonitrile-methanol were used to separate them with high purity degrees. Part of the effluent was monitored with evaporative light scattering detection, for direct control, and the collected fractions were analyzed by thin-layer chromatography, GC, nuclear magnetic resonance spectroscopy and MS. It was thus possible to purify in one run more than 3 g of crude mixture using only 1.31 of solvents to obtain more than 300 mg of several alkylquinolines homologues with 99% purity and in less than 7 h.

STRUCTURE (X-RAY ANALYSIS) OF MANICOLINE B, A MIXTURE OF TWO DIASTEREOISOMERS OF A NEW ALKALOID FROM DULACIA GUIANENSIS (OLACACEAE)

Abstract Manicoline B, isolated from the root bark of Dulacia guianensis (Olacaceae), was shown by X-ray analysis to be an equimolecular mixture of two diastereoisomers of a new alkaloid and to have structure (3).