Antimicrobial activity of compounds from Acanthospermum hispidum DC and Caesalpinia bonduc (L.) ROXB: Beninese plants used by healers against HIV-associated microbial infections.

In this study, we have tested alcoholic extracts (60%) from four Beninese plants: Ocimum gratissimum L., Acanthospermum hispidum DC, Caesalpinia bonduc (L) Roxb and Calotropis procera W. T. Aiton. They are used by the healers to prevent opportunistic diseases associated to HIV-AIDS; on six strains such as: Escherichia coli O 157H7, Staphylococcus aureus ATCC 25923 which resist to methicillin (MRSA), Salmonella typhi, Klebsiella pneumonia, Candida albicans ATCC 10231, and Mycobacterium bovis BCG 040812 which cause microbial infections associated with HIV-AIDS. The results show that all the extracts are bacteriostatic and fungistatic but only the hydro-ethanolic extracts of Acanthospermum hispidum (HE2) and of Caesalpinia bonduc (HE3) presented antibiotic power (respectively ap = 2 and ap = 4) on Candida albicans ATCC 10231. The Mycobacterium bovis BCG shown resistance to tested extracts (CMI > 250 μg/mL). The two fungicidal extracts HE2 and HE3 did not show harmful effects on the cells WI–38 with an IC50 > 100 μg/mL for HE2 and IC50 = 50 μg/mL for HE3. The successive bio-guided purifications of extracts HE2 and HE3 permitted isolation of three antibacterial compounds: Flavanone (M1); stigmasterol (M2); and quercetin (M3). The three isolated compounds possess antibiotic power (ap 3±1) on tested strains and are not toxic on shrimp larvae (LC50: 0.30 ± 0.17 mg/mL).

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.

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).