C. Bories

In Vitro Antileishmanial Activity of Amphotericin B Loaded in Poly(ε-Caprolactone) Nanospheres

The activity of formulations for amphotericin B (AmB) associated with poly (ε -caprolactone) nanospheres and coated with variable amounts of a non ionic surfactant poloxamer 188, was evaluated against AmB-susceptible (WT) and AmB-resistant (AmB r) strains of Leishmania donovani amastigotes in thioglycolate-elicited peritoneal macrophages. AmB-nanospheres were more actives than free AmB only against amastigotes of wild strain. The activity was not influenced by the concentration of poloxamer 188 used to stabilize the nanospheres in spite of this surfactant was previously reported to synergy with AmB on the membrane of the resistant parasite. Similarly, this improvement was not mediated through macrophage activation. In fact, these nanoparticle formulations appeared to inhibit both NO and TNF- α production induced by the free drug. Therefore, we suggest that the association of AmB with nanospheres may improve the capability of the drug to interact with ergosterol. This hypothesis appears to be supported by the fact that nanospheres did not show any improvement of the AmB activity against the resistant strain (characterized by the absence of ergosterol).

Primaquine-loaded poly(lactide) nanoparticles: physicochemical study and acute tolerance in mice

This paper describes the preparation of primaquine loaded-poly (D,L-lactide) nanoparticles. A simple and reproducible method of preparation was developed in chemically soft conditions. The morphological analysis of the colloidal suspension obtained showed a unimodal size distribution, ranging from 150 to 200 nm with a narrow dispersion. The binding of primaquine was highly dependent on pH and drug concentration. The stability of nanoparticles is related to the nature and quantity of hydrophilic and lipophilic surfactants. Intravenously injected primaquine-loaded nanoparticles were well tolerated by healthy and Leishmania donovani-infected mice. The 50% lethal dose of primaquine-loaded nanoparticles was significantly reduced when compared to that of free primaquine.

Selective elution and purification of living Trichomonas vaginalis using gravitational field-flow fractionation

Gravitational field-flow fractionation is one of the simplest separation methods for biological materials. Its potential in parasitology is demonstrated for Trichomonas vaginalis, a parasite responsible for one of the most widespread sexually transmitted diseases. It was observed that this unicellular parasite can be purified in a culture medium with a recovery of 85% for the living trophozoites. The parasite retention characteristics were different when motile living and non-motile dead cells were eluted, motile cells being less retained than the non-motile cells.

Klaivanolide, an antiprotozoal lactone from Uvaria klaineana

Bioguided-fractionation of a CH(2)Cl(2) extract of the stems of Uvaria klaineana (Annonaceae) led to isolation of klaivanolide, a novel bisunsaturated 7-membered lactone (5-acetoxy-7-benzoyloxymethyl-7H-oxepin-2-one), together with benzyl benzoate. Klaivanolide showed potent in vitro antileishmanial activity against both sensitive and amphotericin B-resistant promastigote forms of Leishmania donovani with IC(50) values of 1.75 and 3.12 microM, respectively. The compound also showed in vitro trypanocidal activity against trypomastigote forms of Trypanosoma brucei brucei GVR 35. Its structure was established by 1D and 2D NMR and other spectroscopic techniques.

Unloaded polyisobutylcyanoacrylate nanoparticles: efficiency against bloodstream trypanosomes

The potential use of polyisobutylcyanoacrylate nanoparticles in antiparasitic chemotherapy is described. The nanoparticles on their own proved to have trypanocidal activity against Trypanosoma brucei brucei in‐vitro but not against Trichomonas vaginalis or Entamoeba histolytica. The trypanocidal activity was partly confirmed in‐vivo with T. brucei‐infected mice.

The chitinase system from Trichomonas vaginalis as a potential target for antimicrobial therapy of urogenital trichomoniasis.

Chitinolytic activities in Trichomonas vaginalis membrane extracts were assessed by assays of three enzyme systems: N-acetyl-beta-D-hexosaminidase (NAHase), chitobiosidase and chitotriosidase. N-acetyl-beta-D-hexosaminidase was the enzyme that showed the highest specific activity. After successive subcutaneous inoculations into mice and parasite recovery in culture, the enzyme activities increased significantly with the number of inoculations for up to eight passages. In addition, enzyme activities were maximum at the logarithmic phase of growth. Glycol chitin, a chitinase substrate, enhanced all chitinolytic activities by about 30% and a clear-cut correlation is shown between the capacity for erythrocyte lysis by parasites and NAHase expression. Chitobiosidase and chitotriosidase activities were both inhibited at 58% and 100%, respectively, by allosamidine, a chitinase inhibitor used at 3 microM, whereas NAHase activity was not affected. Seven putative NAHase inhibitors (compounds n, 1-7), ureido and thioureido derivatives of 2-amino-2-deoxy-D-glucose were evaluated and five of them had K(i) values in the range 30-70 microM. The most active compound (compound 6) was functionally competitive with respect to the substrate with a K(i) value of 30 microM. The IC(50) values of the most active compounds on T. vaginalis were in the range 62-85 microM. These results indicate that chitinases of T. vaginalis are involved in pathogenicity and they could be an interesting target for drugs since chitinase inhibitors also inhibit parasite growth.

Isolation of microfilariae from blood by gravitational field-flow fractionation

Over 100 million persons suffer from diseases caused by filariae infestation, and one billion are at risk. A simple isolation method for both analytical and preparative separation is presented. Based on the simplest field-flow fractionation technique, the gravitational one, effective isolation of microfilariae is achieved. Microfilariae are eluted in the void volume of the channel without pollution by red blood cells. The red blood cell elution peak shows a total absence of microfilariae, as demonstrated after fraction collection and microscopic investigation. The elution mode of microfilariae and red blood cells appears to be a steric one, as confirmed by a reinjection experiment. The simplicity, low cost and the relatively short time required for this separation (10 min) indicate that gravitational field-flow fractionation could become a new separation tool for screening of microfilariae. With both live and dead microfilariae, the high recovery (66-80%) allows preparative fractionation for diagnostic purposes or fundamental research.

Synthesis and nematocidal activities of new analogs of pyrantel

Summary A set of new analogs of pyrantel was synthesized in good yields by lithiation of 1,2-dimethyltetrahydropyrimidine with n -butyllithium in tetrahydrofuran and condensation with aromatic esters. Spectrometric studies showed the large influence of intramolecular bonding in the tautomeric equilibria between the possible structures. Anthelmintic screening showed in vitro efficiency against Molinema dessetae , but a weak activity against Rhabditis pseudoelongata and Nippostrongylus brasiliensis .

Synthesis, antifungal and nematocidal activities of thioureines with an aminoester sequence

Twenty-three arylthioureines bearing β-alanine or γ-aminobutyric alkyl ester chains were synthesized for in vitro screening toward 44 strains of fungi and 2 genera of nematodes. The nitro derivatives were the most potent compounds against Aspergillus and Candida strains. Ester chains increase activity against the filarial worm Molinema dessetae. Twelve compounds have EC 50 < 40 μg/ml. However, the anthelmintic potency is weak compared with tetramisole

Une nouvelle classe de composés anti-parasitaires: les spiroarsoranes. Evaluation in vitro sur la filaire Molinema dessetae

Resume Une nouvelle classe de composes biologiquement actifs, les «spiroarsoranesa a ete synthetisee et leur activite testee in vitro sur la filaire Molinema dessetae . Une importante activite filaricide a pu etre ainsi demontree, avec une faible toxicite.