Functional derivatives of 5-benzo[1, 3]dioxol-5-yl-1-methyl-1H-imidazole-2-carbaldehyde and evaluation of leishmanicidal activity.

New imidazole derivatives were obtained after subjecting 5-benzo[1, 3]dioxol-5-yl-1-methyl-1H-imidazole-2-carbaldehyde to a Knoevenagel reaction. Some of these compounds exhibit significant in vitro leishmanicidal activity.

Evaluation of in-vitro leishmanicidal activity of hydrazones of thiophene carboxaldehydes against promastigotes of Leishmania infantum and Leishmania tropica.

The lack of leishmanicidal drugs has prompted the synthesis and testing of new hydrazones of thiophene carboxaldehydes against three Leishmania strains. The compounds were obtained by condensation of appropriate hydrazines with thiophene 2-carboxaldehyde (series 1), thiophene 3-carboxaldehyde (series 2), and 5-nitrothiophene-2-carboxaldehyde (series 3). Leishmanicidal activity was assessed against promastigotes of Leishmania strains, grown in-vitro in nutrient broth medium complemented with fresh rabbit blood. The minimal inhibitory concentrations were evaluated against pentamidine, as a reference drug. Several compounds exhibited significant leishmanicidal activity, the best being ten times more active than pentamidine.

Studies on antiparasitic agents: effect of the lactam nucleus substitution in the 2-position on the in-vitro activity of new 5-nitroimidazoles.

The in-vitro antiprotozoal activity of a series of new 5-nitroimidazoles substituted in the 2-position via a lactam nucleus was studied. All these compounds exhibited a better effect than metronidazole and structure-activity relationships are discussed.

Anthelmintic properties of Polygonum glabrum.

A pure anthelmintic substance (PGA) has been isolated from the methanol-aqueous extract of the leaf of Polygonum glabrum Willd., a semi-aquatic Sudanese species of the family Polygonaceae. The antiparasitic in-vitro activity of several fractions isolated from the plant, has been examined comparatively with that of PGA. PGA also showed molluscicidal activity against Biomphalaria glabrata and Limnea truncatula Müll. Structural determination of PGA was attempted following data analysis of UV, IR, 13C NMR, 1H NMR and MS spectra and suggests that PGA is a terpenoid.

Ethnobotanical survey and in vitro antiplasmodial activity of plants used in traditional medicine in Burkina Faso.

In Burkina Faso, most people in particular, in rural areas, use traditional medicine and medicinal plants to treat usual diseases. In the course of new antimalarial compounds, an ethnobotanical survey has been conducted in different regions. Seven plants, often cited by traditional practitioners and not chemically investigated, have been selected for an antiplasmodial screening: Pavetta crassipes (K. Schum), Acanthospermum hispidum (DC), Terminalia macroptera (Guill. et Perr), Cassia siamea (Lam), Ficus sycomorus (L), Fadogia agrestis (Schweinf. Ex Hiern) and Crossopteryx febrifuga (AFZ. Ex G. Don) Benth. Basic, chloroform, methanol, water-methanol and aqueous crude extracts have been prepared and tested on Plasmodium falciparum chloroquine-resistant W2 strain. A significant activity has been observed with alkaloid extract of P. crassipes (IC(50)<4 microg/ml), of A. hispidum, C. febrifuga, and F. agrestis (4

Synthesis and study of antiprotozoal activity of some 5-nitrothiophene aldimines.

This paper reports on the synthesis and the antiparasitical activity of some 5-nitrothiophene aldimines variously substituted on aniline nucleus. The influence of substituents on the activity of the prepared compounds is discussed.

New pyrazolo[3,4-b]pyrazines: synthesis and biological activity.

Some new pyrazolo[3,4-b]pyrazines and related heterocycles were synthesized and evaluated for their antifungal and antiparasitic activities. The key intermediate, 6-amino-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyrazine-5-carbonitrile (3) was obtained in a one-pot synthesis via the reaction of 5-amino-3-methyl-4-nitroso-1-phenylpyrazole 2 with malononitrile.

[Long-term treatment of Alzheimer's disease: followup of a cohort of 255 patients treated with lacrine for four years]. / Traitement de la maladie d'Alzheimer au long cours: à propos d'une cohorte de 255 patients traités quatre ans par tacrine.

We describe the follow-up of a cohort of 255 Alzheimer's disease (AD) patients (81 males, 174 females) treated by tacrine during 4 years. We performed the survey of hepatic, cholinergic and general tolérance. Drug efficacy was measured by MMS examination on weeks 0, 18, 30, 52, 104, 156 and 208. A total of 190 patients (74.5 percent) were dropped out of this study, 75 (29 percent) for adverse events. We found 85 hepatic (33 percent), 79 cholinergic (31 percent), 31 (12 percent) neuropsychiatric and 72 general (28 percent) side effects. In term of drug efficacy we observed a global decline of 2.5 MMS points during the first year and 2 MMS points between W52 and W156. Tacrine's symptomatic efficacy, defined as the number of patients improved or stabilized at W30, was present in 50 patients (46 percent) among the 109 patients reaching W30. The intensity of symptomatic efficacy was expressed by a 2.7 MMS points increase in 37 patients improved on W30. The long term effects of Tacrine, measured by the MMS score at one year, showed a positive impact as the MMS was 2.5 points above the expected score in non treated AD patients. This study raises the practical problem of optimal cholinesterase inhibitors use in AD and the theoretical question of long term action of cholinesterase inhibitors on cerebral lesions of AD.

No evidence of oxidant events in amphotericin B cytotoxicity versus L. infantum promastigotes.

Amphotericin B is used for the treatment of systemic mycoses and visceral leishmaniasis. The objective of our study was to evaluate the impact of catalase, ascorbic acid and ketoconazole on the amphotericin B toxicity towards Leishmania promastigotes membrane by two flow cytometric tests, the membrane potential assay using a cationic dye, [DiOC5(3)], and the membrane permeability test using propidium iodide. The collapse of membrane potential appeared at amphotericin B concentrations weaker than those assessed by the membrane permeability test. The binding of amphotericin B to membrane sterol was not modified by catalase or ascorbic acid whereas amphotericin B-induced growth inhibition could be modulated by these products. The permeabilizing effect of amphotericin B on parasite membrane was strongly reduced in the presence of ketoconazole. These results confirmed the pore hypothesis of amphotericin B action and suggested that flow cytometric methods constituted a valuable alternative to conventional methods for assessing the effect of drugs on cellular membrane and evaluating parasite susceptibility to polyene antibiotics.

[Balance sheet of tolerance-efficacy on the use of tacrine in 100 cases of Alzheimer's disease]. / Bilan tolérance-efficacité d'un an d'utilisation de la tacrine dans 100 cas de maladie d'Alzheimer.

We report our first 100 cases of Alzheimer's (AD) patients treated with tacrine (Cognex) for a period of one year. At the beginning of treatment the mean Mini-Mental-Status (MMS) score was 15.1. To date 71 patients are still under treatment (12 for more than 12 months). Forty-three instances of side-effects were observed, of which 31 involved hepatic side-effects with an increase in ALAT > IN (normal value) (6 cases > 3N), the mean date of appearance was 10.4 +/- 6.8 weeks, there were 16 cholinergic side-effects (nausea, vomiting, diarrhoea), plus 4 neurologic and 2 cutaneous side-effects. These side-effects led to the arrest of the treatment in 19 cases (16 for hepatic toxicity). Treatment was reattempted after interruption in 13 cases; successfully in 3 instances only. The measure of tacrine efficacy was based on 52 MMS score re-evaluations in week 18: there was an increase of the MMS score in 22 cases (3.3 points +/- 2.5), a stabilisation in 11 cases and a decrease in 19 cases (3.3 points +/- 2.2.). In week 30, the MMS scores (35 patients) increased in 9 cases (3.6 points +/- 2.4), stabilized in 5 cases and decreased in 21 cases (3.9 points +/- 3.3). At week 52, only 28 per cent of the patients were considered as either improved or stabilized. We conclude that there is a necessity for close follow-up of tacrine-treated patients, and that globally at 8 months there is an improvement or a stabilization in 40 per cent of patients and long term (at one year) a stabilizing effect on AD patients.

[Double contrast studies of the colon. Use of acetyl-cystein or mucofluid? (author's transl)]. / Double contraste colique. Acétyl-cystéine ou mucofluid?

The authors propose a replacement product for acetylcysteine which had been suggested for use in order to obtain good double contrast studies of the colon after retrograde barium introduction. Mucofluid gives even better results at a much lower cost.

[Comparative study of fungicidal activity in vitro of various quaternary ammonium compounds used in ophthalmology]. / Etude comparée de l'activité antifongique in vitro de quelques ammoniums quaternaires utilisés en ophtalmologie.

A study was conducted to evaluate the antifungal activity in vitro of 5 quaternary ammonium compounds. N cetylpyridinium was found to be particularly active against Candida albicans and Aspergillus fumigatus. The association of N cetylpyridinium and of neosynephrine, found in various eye drop compositions, resulted in potentation of the antifungal activity of this quaternary ammonium.

Evaluation of the antimalarial activity of new compounds against Plasmodium falciparum in vitro, and Plasmodium berghei in vivo.

Various hydrazones of thiophene carboxaldehyde were tested in vitro on two Plasmodium falciparum strains and in vivo on mice experimentally infected with Plasmodium berghei. These hydrazones were obtained by condensation of appropriate hydrazines with thiophene-2-carboxaldehyde (series 1), thiophene-3- carboxaldehyde (series 2) and 5-Nitrothiophene-2-carboxaldehyde (series 3). Compounds of series 3, 5-Nitrothiophene-2-carboxaldehyde presented significant effects in vitro. In vivo tests confirmed the antimalarial activity observed in vitro with two compounds of this series.

Flow cytometry to evaluate the parasitemia of Plasmodium falciparum.

The resistance of plasmodiums to the current antimalarial agents has spurred the search for new active molecules of vegetal origin or chemical synthesis. The screening of antimalarial molecules "in vitro" was done by simple but tedious techniques such as quantification of parasitemia through optical microscopy or by using radioactive markers. We have developed a new method to evaluate parasitemia by using the ODAM ATC 3000 flow cytometer and biological cell sorter. We selected the ethidium bromide for labelling the nucleic acids of Plasmodium falciparum, and we optimised the method by using a mathematical model: the design of Hadamar. This simple technique presents the advantage of being an objective and rapid count of large number of red cells (10(6) x 10(7)). This method is rapid, reliable, reproducible, devoid of subjectivity and provides more precise results than those of optical microscopy. The good correlation between paraitemia measured by optical microscopy and fluorescence obtained by flow cytometry allows us to recommend this technic for the screening of new antimalarial molecules.

3-Aminorhodanine and 2-hydrazino-2-imidazo-line hydrazones. Synthesis and antiparasitic pharmacology.

Two series of hydrazones were prepared by condensation of various aldehydes with 2-aminorhodanine (series 1) and 2-hydrazino-2-imidazoline (series 2). These compounds showed interesting antiparasitic activities against amoeba, trichomonas, leishmania and plasmodium.