Natural Products from Cameroonian Medicinal Plants

Sammanfattning: Natural product chemistry is a main research area in Cameroon, as well as for the division of Bioorganic Chemistry at Lund Institute of Technology. A review of the results obtained recently with Cameroonian medicinal plants shows that a large number of compounds, many with complex structures, have been isolated and characterised, and the work presented in this thesis is part of this effort. Based on empirical, ethnodietary, and ethnomedicinal information obtained from medicine men who use the plants to treat various diseases, several species were collected for study. Extraction, fractionation and purification using various chromatographic techniques led to the isolation and characterisation of a large number of compounds including several novel derivatives. Structure elucidation was achieved by a combination of spectroscopic techniques (NMR, UV, IR, MS). Biological tests performed on some of the isolated compounds showed some promising results. Sesquiterpenes obtained from Reneilmia cincinnata were tested against two Plasmodium falciparum clones; the Indochina W-2 clone, resistant to chloroquine, pyrimethamine, sulfadoxine, and quinine; and the Sierra Leone D-6 resistant to mefloquine. Plasmodium species are parasites that cause life-threatening diseases, four related species, P. falciparum, P. malariae, P. ovale, and P. vivax, are responsible for human malaria. P. falciparum, the most virulent malaria parasite, is responsible for more than one million deaths per year while hundreds of millions of cases of malaria occur annually. R. cincinnata was identified in a preliminary screening as a potential antimalarial plant. The isolated sesquiterpenes were then tested against the most virulent parasite. Inhibition concentrations (IC50) of the range 1.5-1.6 ug/ml for D-6 and 1.9-31.9 ug/ml for W-2 were determined. Similar activities were noted with diarylheptanoids isolated from Aframomum letestuianum when tested against three major strains of Trypanosoma brucei, a causative agent of African trypanosomiasis or sleeping sickness. The three strains were Lab 110 EATRO, a drug sensitive strain of Trypanosoma brucei brucei; KETRI 243, an uncloned clinical isolate of Trypanosoma brucei rhodesiense; and KETRI 243 As-10-3 a pentamidine and melarsol-resistant clone of Trypanosoma brucei rhodesiense. In addition, chemical studies were performed with aframodial, an alpha,beta-unsaturated dialdehyde and major component of some Aframomum species. It turned out to be very reactive toward amines and amino acids, and several pyrrole and oxazolidine derivatives were prepared.