Synthesis and in vitro antikinetoplastid activity of polyamine-hydroxybenzotriazole conjugates.

Thirteen new polyamine derivatives coupled to hydroxybenzotriazole have been synthesized and evaluated for their in vitro antikinetoplastid activity. Trypanosoma Trypanothione reductase (TryR) was envisioned as a potential target. Among all tested molecules, only one compound, a N-spermidine-benzotriazole derivative, displayed relevant inhibitory activity on this enzyme but was not active on parasites.

Design, synthesis and in vitro antikinetoplastid evaluation of N-acylated putrescine, spermidine and spermine derivatives.

A structure-activity relationship study on polyamine derivatives led to the synthesis and the determination of antikinetoplastid activity of 17 compounds. Among them, a spermidine derivative (compound 13) was specifically active in vitro against Leishmania donovani axenic amastigotes (IC50 at 5.4μM; Selectivity Index >18.

New potent bisubstrate inhibitors of histone acetyltransferase p300: design, synthesis and biological evaluation.

Bisubstrate-type compound Lys-CoA has been shown to inhibit the p300 histone acetyl transferase activity efficiently and may constitute a lead compound for a novel class of anticancer therapeutics. Based on this strategy, we synthesized a series of CoA derivatives and evaluated these molecules for their activity as p300 histone acetyltransferases inhibitor. The best activity was obtained with compound 3 bearing a C-5 spacing linker that connects the CoA moiety to a tert-butyloxycarbonyl (Boc) group.

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.

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.