Antitrypanosomal alkaloids from Polyalthia suaveolens (Annonaceae): their effects on three selected glycolytic enzymes of Trypanosoma brucei.

In continuation of our study on medicinal plants of Cameroon, stem barks of Polyalthia suaveolens were phytochemically studied. This investigation yielded a new indolosesquiterpene alkaloid, named polysin (1) and four hitherto known alkaloids (2-5). Polysin (1) appeared as a competitive reversible inhibitor (K(i)=10 microM) of phosphofructo kinase (PFK) of Trypanosoma brucei with respect to fructose-6-phosphate (K(i)/K(M)=0.05) and could be used in the design of new trypanocidal drugs. The other isolated compounds (2-5) also exhibited interesting inhibitory effects on selected glycolytic enzymes (PFK, glyceraldehyde-3-phosphate dehydrogenase and aldolase).

Antitrypanosomal and cytotoxic activities of 22-Hydroxyclerosterol, a new sterol from Allexis cauliflora (Violaceae).

In the search for new antiparasitic natural compounds from the medicinal plants from Cameroon, the new 22-hydroxyclerosterol, established as such on the basis of detailed chemical and spectroscopic analysis, was isolated from the hexane extract of the stem bark of Allexis cauliflora together with the known clerosterol. 22-Hydroxyclerosterol inhibited the growth of Trypanosoma brucei brucei cells with an ED(50) value of 1.56 µM. The compound was also established as an uncompetitive inhibitor of the glycolytic enzyme PGI of T. brucei (Ki'= 3 ± 1 µM), an uncompetitive inhibitor of mammalian rabbit muscles' enzyme PyK (Ki'= 26 ± 3 µM) and a mixed inhibitor of PyK of Leishmania mexicana (Ki'= 65 ± 10 µM; Ki= 24 ± 5 µM).

Uapaca genus (Euphorbiaceae), a good source of betulinic acid.

Betulinic acid, isolated in substantial amounts from stem barks of five distinct species of Uapaca could be considered as an important chemotaxomic marker of the Uapaca genus. It inhibited Trypanosoma brucei GAPDH with an IC(50) value of 240 microM and has been shown to be a competitive reversible inhibitor (Ki=200+/-10 microM) of this enzyme with respect to its cofactor NAD(+).

Antitrypanosomal activity of polycarpol from Piptostigma preussi (Annonaceae).

Polycarpol, sitosterol and sitosterol-3-O-beta-D-glucoside isolated for the first time from Piptostigma preussi (Annonaceae) occur regularly in some Annonaceae such as Piptostigma genus. Polycarpol exhibits interesting antitrypanosomal activity with an ED(50) value of 5.11 microM on Trypanosoma brucei cells. Moreover, it inhibits T. brucei glycolytic enzymes GAPDH and PFK with IC(50) values of 650 and 180 microM respectively.

In vitro inhibitory effects of palmatine from Enantia chlorantha on Trypanosoma cruzi and Leishmania infantum.

In an attempt to establish the components responsible for the use of Enantia chlorantha against cutaneous leishmaniasis in local traditional medicine, a well-known palmatine has been isolated in substantial amounts from a methanolic bark extract of this plant species. Palmatine therein obtained exhibited a significant inhibitory activity on growth of both Trypanosoma cruzi (IC(50) 0.068 microM) and Leishmania infantum (IC(50) 0.79 microM).