Leishmanicidal activity of Maytenus illicifolia roots.

In vitro evaluation of leishmanicidal activity of aqueous and ethanolic extracts of Maytenus illicifolia against three species of Leishmania. The root extracts showed differential activity against parasites, whereas the aerial part of the extracts was inactive.

Screening of New Caledonian and Vanuatu medicinal plants for antiprotozoal activity.

Sixty-seven extracts of 30 medicinal plants traditionally used in New Caledonia or Vanuatu by healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro for their antiprotozoal activity against Leishmania donovani, Leishmania amazonensis and Trypanosoma cruzi. Among the selected plants, Pagiantha cerifera was the most active against both Leishmania species; four extracts were active against promastigotes of Leishmania donovani at EC(50) values inferior to 5 microg/ml. Garcinia pedicillata extract had an EC(50) value of 12.5 microg/ml against intracellular amastigotes of Leishmania amazonensis. Alone Amborella trichopoda reduced by more of 80% the trypomastigotes of Trypanosoma cruzi in the blood.

Cryptofolione derivatives from Cryptocarya alba fruits.

Cryptofolione (1) and the new cryptofolione derivative 6-(4,6-dimethoxy-8-phenyl-octa-1,7-dienyl)-4-hydroxy-tetrahydro-pyran-2-one (2) were isolated from the fruits of Cryptocarya alba. The structures were elucidated by spectroscopic methods. Cryptofolione showed activity towards Trypanosoma cruzi trypomastigotes, reducing their number by 77% at 250 microg mL(-1). Cryptofolione showed moderate cytotoxicity in both macrophages and T. cruzi amastigotes. It also displayed a mild inhibitory effect on the promastigote form of Leishmania spp. As both cytotoxic and trypanocidal effects are similar, the compound presented little selectivity in our assay models.

Activity of compounds isolated from Chilean lichens against experimental cutaneous leishmaniasis.

Three secondary metabolites isolated from Chilean lichens, (+) usnic acid, pannarine and 1'-chloropannarine, were tested against promastigotes forms of three strains of Leishmania ssp. Pannarine and 1'-chloropannarine exhibited in vitro activity at 50 micrograms/ml and (+) usnic acid at 25 micrograms/ml. BALB/c mice infected with Leishmania amazonensis were treated 4 weeks post-infection with (+) usnic acid by subcutaneous or oral routes for 15 days at 25 mg/kg or by five intralesional injections at interval of 4 days at 25 mg/kg of body weight. The reference drug, N-methylglucamine antimonate (Glucantime), was administered by subcutaneous injections (regimens of 28 mg of pentavalent antimony) for 15 days. The subcutaneous and oral treatments with (+) usnic did not produce any effect, but by intralesional administration we observed a significant effect that reduced by 43.34% the weight lesions and by 72.28% the parasites loads in infected footpads.

Seroprevalence and sociocultural conditionants of Chagas disease in school-aged children of marginal zones of Asunción.

Chagas disease is becoming a public health problem in Latin America due to the wide distribution, the high prevalence, the magnitude of the damage caused and the difficulties to control it. In Paraguay, the disease is mainly distributed in the departments of Paraguarí, Cordillera and Central. Prevalence in marginal zones, where migrations from rural populations and endemic areas make possible the urbanization of the disease, has no been studied yet. This is a descriptive study with a cross-sectional sampling and a probabilistic system recruitment carried out in school aged children from marginal zones of Asunción to determine the prevalence of Chagas' disease. Serological methods, parasite isolation and questionnaires were used to achieve the goals. Nine hundred and fifty three children were studied to determine the prevalence of Chagas' disease in marginal zones which was 1.4%.

New prenylated quinones from Peperomia galioides.

Two new prenylated quinones, piperogalone (1) and galopiperone (2), and a new prenylated dihydroquinone, hydropiperone (3), were isolated from Peperomia galioides H.B.K (Piperaceae). Hydropiperone exhibited potent antiparasitic activity against three species of Leishmania.

Synthesis and in vitro antiprotozoal activity of thiophene ring-containing quinones.

A series of quinones (3a-i, 4-9, 11) and aromatic compounds (2a, 2d, 2g) containing the thiophene ring were tested in vitro against the trypomastigote form of Trypanosoma cruzi and the promastigote forms of Leishmania. The quinones 3a-i, 4, 5a, b, 6 and 9 having the thiophene ring fused to a quinone nucleus were the most active members of the series. The electron affinities of the benzo[b]thiophene-4,7-quinones 3, evaluated by their LUMO energies and halfwave potentials, are reported.

Characterization of Paraguayan Trypanosoma cruzi strains isolated from acute patients of Chagas disease.

Five Paraguayan Trypanosoma cruzi strains, isolated from acute chagasic patients, were studied by their behavior in BALB/c mice, metacyelogenesis, bio-metry of metacyclic forms and lectin agglutination. Early and intermediate parasitemic peaks were observed and the strains did not show high virulence. Metacyclogenesis capacity was not higher than 50% in all cases and there were no considerable differences in the biometry. They all belong to WGA-type strains according to the lectin agglutination assays except for one strain that agglutinated with WGA and PNA lectins. Although previous schizodeme analysis of these strains showed rather homogeneous profiles, biological features were quite heterogeneous.

In vitro and in vivo leishmanicidal studies of Peperomia galioides (Piperaceae).

Petroleum ether and methylene chloride extracts of Peperomia galioides and three prenylated diphenols, grifolic acid, grifolin and piperogalin exhibited in vitro antileishmanial activity. During the course of infection of BALB/c mice with Leishmania amazonensis, the treatments with each of these compounds did not influence the progression of the disease.

New aporphine alkaloids from guatteria foliosa.

Four new alkaloids were obtained from Guatteria foliosa, namely, the noraporphines (-)-3-methoxyputerine [1] and (+)-norguattevaline [2], the more highly oxidized (+)-3-methoxyguattescidine [3], and the oxoaporphine 3-methoxyoxoputerine [4]. Among several other known alkaloids also found in this same plant, (-)-3-hydroxynornuciferine, (-)-isoguattouregidine, and argentinine exhibited significant activity against Trypanosoma cruzi.

Leishmanicidal activity of combretastatin analogues and heteroanalogues.

We have investigated the in vitro leishmanicidal activity of representative members from series II-V of combretastatin analogues and heteroanalogues. Most of them exhibited different degrees of activity against various strains of Leishmania spp. The diaryl(heteroaryl)ethane system or the more complex fused heterocyclic stilbenoids, constitute useful skeletal bases to support some kind of antiparasitic activity. Particularly, the incorporation of 2-furyl substituents led to potent antileishmanial compounds, which have been selected for in vivo testing on murine models.

Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase.

Eleven bisbenzylisoquinoline (BBIQ) alkaloids were studied for in vitro trypanocidal activity against trypomastigote forms of the Y strain of Trypanosoma cruzi. The inhibitory activity of these compounds against trypanothione reductase (TR), a target enzyme for chemotherapy against Chagas disease, was also studied. Six BBIQ alkaloids (antioquine, cepharanthine, daphnoline, limacine, cycleanine and (-) curine) displayed a 50% lethal concentration (LC50) against T. cruzi of less than 100 microM. Daphnoline and curine, with LC50 values of 10 microM, are attractive for further investigation as potential anti-Chagasic drugs. Kinetic analyses suggested the BBIQ alkaloids are mixed inhibitors of TR. These compounds are reasonably potent inhibitors of TR; the best TR inhibitor, cepharanthine, had an IC50 of 15 microM, which is in the same order of magnitude as its LC50 against T. cruzi. The similar magnitudes of the IC50 and LC50 values suggest that inhibition of TR could contribute to the trypanocidal activity exhibited by the BBIQ alkaloids.

Acetogenins and other compounds from Rollinia emarginata and their antiprotozoal activities.

Bioactivity-directed fractionation of the MeOH extract of the stem barks of Rollinia emarginata resulted in the isolation of six compounds, four acetogenins, rolliniastatin-1, sylvaticin, squamocin, and rollidecin B, one lignan, lirioresinol B, and an oxoaporphine, liriodenin. Their structures were determined by spectroscopic analysis and their in vitro leishmanicidal and trypanocidal properties are reported.