Xylopioxyde and other bioactive kaurane-diterpenes from Xylopia aethiopica Dunal (Annonaceae).

A new cytotoxic ent-kaurane-type diterpene named xylopioxyde (16,17-epoxy-15-oxo-ent-kauran-19-oic acid) has been isolated from the fruits of Xylopia aethiopica Dunal (Annonaceae) together with three known compounds, namely 15α-acetoxy-ent-kaur-16-en-19 oic acid (xylopic acid), 15-oxo-ent-kaur-16-en-19-oic acid and ent-kaur-16-en-19-oic acid. Xylopic acid, obtained in a good amount, has been successively converted in moderate to good yields into 15-hydroxy-ent-kaur-16-en-19-oic acid, 15-oxo-ent-kaur-16-en-19-oic acid and two new selective trypanocidal stereoisomers of 15-acetoxy-16,17-ent-epoxy-kauran-19-oic acid, respectively. All the compounds except the synthetic epoxides displayed cytotoxic effects on the mammalian fibroblast cell line MRC-5 as well as inhibitory effects on the growth of the bloodstream forms of Trypanosoma brucei brucei cells (strain 241).

Synthesis, characterization, anti-trypanosomal activity and toxicity against Artemia salinaLeach of thiobenzamides and derivatives.

This work aims to synthesize, characterize of thioamides benzaldehyde and 4- (dimethylamino)benzaldehyde and assess their in votrotrypanocidal activity and totoxicity. The Willgerodt-Kindler reaction preferred for the synthesis of thioamides morpholin-4-yl (phenyl) methanethione 1 and [4 - (dimethylamino) phenyl] - (morpholin-4-yl) methanethione 2, is catalyzed with montmorillonite K-10 and in a microwave oven. The structures of the thioamides were characterized and confirmed by IR spectrometry, nuclear magnetic resonance (1H and 13C NMR) and mass spectrometry (MS) Their trypanocidal activity was evaluated in the blood stream form of the strain of Trypanosoma brucei brucei 427 using the "Lilit, Alamar Blue" (Baltz et al., 1985; Hirumi et al., 1994; Räz et al., 1997) and cytotoxicity on brine shrimp larvae (Artemia salina Leach) using the method of Michael et al. (1956) resumed by Vanhaecke et al. (1981) and Sleet and Brendel (1983). The compounds1 (IC50> 483.09 M) and 2 (IC50> 400 M) have weak trypanocidal activities. However the larvae were sensitive to 2 (LD50 = 214 ± 9 M) and therefore it could be used in cancer treatment.

Synthesis, characterization and anti-trypanosomal activity of R-(-)carvone and arylketones-thiosemi carbazones and toxicity against Artemia salina Leach.

This work is focused on the synthesis and characterization of a series of N(4)- substituted thiosemicarbazones and the evaluation of their in-vitro anti-trypanosomal activity and toxicity. A series of thiosemicarbazones (1-4) and N(4)-phenyl-3-thiosemicarbazones (5-8) have been synthesized on R-(-)carvone, acetophenone, 4’-methylacetophenone and benzophenone by condensation reaction with good yields. All compounds were characterized by spectrometrical analysis methods infrared IR, nuclear magnetic resonance NMR (1H &13C) and mass spectrometry MS, confirming their structures respectively, and were evaluated for their invitro parasitic activity against the bloodstream form of the strain 427 of Trypanosoma brucei brucei using the “LILIT, Alamar Blue” method (Baltzet al., 1985; Hirumi et al., 1994; Räz et al.,1997). Their toxicity against brine shrimp larvae (Artemia salina Leach) was studied, according to the method of Michael et al. (1956) resumed byVanhaecke et al. (1981) and bySleet and Brendel (1983). Some of them have exhibited a strong trypanocidal activity, especially compounds 8, 3, 1 and 4 with their half-inhibitory concentrations (IC50) values equal to 8.48, 8.73, 39.71 and 67.17 micro-molar (μM) respectively. Except compounds 1 and 4whose half-lethal concentration (LC50) values were20.58 and 33.72 μM respectively and then toxics, all synthesized compounds showed negligible toxicity against Artemia salinaL. (LC50> 280 μM) and good selectivity (S) (SI “index” ≤1).