Synthesis and trypanocidal activity of salicylhydrazones and p-tosylhydrazones of S-(+)-carvone and arylketones on African trypanosomiasis.

Hydrazones are nowadays considered to be good candidates for various pharmaceutical applications. Here, we have synthesized two series of hydrazones: salicylhydrazones (GS1-4) and p-tosylhydrazones (GT1-4) from S- (+)-carvone and three aryketones with good yields (57-91%). Molecules were characterized by elemental analyses; TLC, NMR 1H, NMR 13C and MS. Submitted, in vitro, to their antiparasitic testing on Trypanosoma brucei brucei, and toxicity on Artemia salina Leach, all compounds except GT2 showed significant antitrypanosomal activity IC50 ranging from 1 to 34 micromolar (μM). Among them, 2-acetynaphthalene salicylhydrazone GS4 (IC50 = 1.97 ± 0.42 μM) and 7-methoxy-1-tetralone p-tosylhydrazone GT3 (IC50 =7.98 ± 1.65 μM) exhibited good trypanocidal activity and the other are moderates on parasite; when the compounds GS1, GT3 and GT4 presented toxic activity on larvae. In agreement to their selectivity index, which is greater than 1 (SI > 1), products turn out quite selective on the parasite: a series of salicylhydrazones revealed more selective (SI ≥ 11), especially GS4 (SI = 157) than the series of p-tosylhydrazones showed 1 ≤ SI ≤ 22. The synthesized compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. Compounds developing could open promising route to news drug-candidates.

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.

Antihemolytic Properties of Extracts of Six Plants Used in the Traditional Treatment of Sickle Cell Disease in Benin.

This study is focused on the in vitro evaluation of the hemolysis inhibitory activity of aqueous extracts of six plants used in the traditional treatment of sickle cell disease in Benin: Morinda lucida, Uvaria chamae, Lonchocarpus cyanescens, Croton zambesicus, Raphiostylis beninensis and Xylopia aethiopica. AS and SS red blood cells are subjected to hyposmotic impact with decreasing concentrations of NaCl solution. All the aqueous extracts of the six plants showed a better contribution in erythrocyte osmotic resistance from the concentration of 5 mg/mL to 1 mg/mL, except the extract at 5 mg/mL of Raphiostylis beninensis that caused hemolysis of both red blood cells AS and SS. The extract at 1 mg/mL of Raphiostylis beninensis and the extracts at 5mg/mL of Xylopia aethiopica and Croton zambesicus showed a high hemolysis inhibition of red blood cells AS and SS. The extracts of Lonchocarpus cyanescens showed moderate hemolysis inhibition of SS red blood cells while extracts of Uvaria chamae inhibited highly the hemolysis of AS red blood cells. As for the roots of Morinda lucida, only the extract at 5mg/mL highly inhibited the hemolysis of the AS red blood cells. This protocol seems appropriate to work with both AS and SS blood because the comparative effects of each tested extract on hemolysis of AS and SS blood showed a good correlation coefficient of Pearson (1 or -1). All the plants tested in this work showed, at different doses, an in vitro antisickling effect and this explains partially their use in the traditional treatment of sickle cell disease.

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).