Leishmanicidal activity of two canthin-6-one alkaloids, two major constituents of Zanthoxylum chiloperone var. angustifolium.

The crude alkaloidal extract of Zanthoxylum chiloperone stem bark exhibited in vitro activity against various strains of Leishmania ssp. at 100 microg/ml. Two active major constituents were isolated and identified as canthin-6-one and 5-methoxycanthin-6-one. The effect of these compounds was also tested in an in vivo assay using BALB/c mice infected with Leishmania amazonensis. The mice were treated for 5 weeks postinfection with these alkaloids by oral (14 days) or intralesional route (4 days) at 10 mg/kg daily. The reference drug, N-methylglucamine antimonate was administered by subcutaneous injections at 100 mg/kg for 10 days. Intralesional administration of canthin-6-one reduced the parasite burden but not significantly when it was compared with the untreated group, while the reference drug reduced by 91% the parasite loads in the lesion.

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.

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.

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.

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.

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.

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.

Mutagenicity, insecticidal and trypanocidal activity of some Paraguayan Asteraceae.

The insecticidal, moulting inhibition and trypanocidal effects of crude extracts of 7 Paraguayan Asteraceae were evaluated on Triatoma infestans and bloodstream forms of Trypanosoma cruzi, respectively. Both mutagenicity and toxicity were evaluated by sister chromatid exchange (SCE) in human peripheral lymphocyte culture and by the lethality test of Artemia salina. The ethanolic extracts from Chromolaena christieana (stem and bark), Achyrocline satureoides (leaves and flowers) and Mikania cordifolia (root and stem), at a concentration of 250 micrograms/ml, showed the highest percentage of lysis on bloodstream forms of Trypanosoma cruzi. The extracts of Chromolaena christieana and Achyrocline satureoides also presented high mutagenic and toxic capacity when they were evaluated by the SCEs assay and Artemia salina test, respectively. Insecticidal activity was only observed in the hexane extract of flowers of Achyrocline satureoides (45% of mortality), when 0.05 microgram of crude concentration was applied on Triatoma infestans. The ethanolic extracts of stem from Mikania cordifolia and Vernonia brasiliana inhibited the moulting of Triatoma infestans when it was compared with their controls. Since no ethnobotanical information on these plants has been found related to similar use in Paraguay, our findings suggest, for the first time, the potential anti-trypanocidal and moulting inhibition of these Asteraceae.

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.

Prevalence of Chagas' disease in Ayoreo communities of the Paraguayan Chaco.

The prevalence of Chagas' disease in Ayoreo amerindians living in their traditional habitat of the Paraguayan Chaco was assessed by ELISA and indirect immunofluorescence techniques. The Ayoreo is the last hunther-gatherer tribe of the Paraguayan Chaco and was "pacified" between 1965 and 1975. They still maintain a seminomadic way of life. Chagas' disease prevalence in the Ayoreo communities probably represents their natural prevalence in Chaco Amerindians before settlement. Triatoma sordida was identified as the insect vector in the settlements of Gesudi and Chovoreca, while the highly domiciliary Triatoma infestans was found in Campo Loro. The prevalence of Chagas' disease in Gesudi and Chovoreca, based on our serological surveys was 12-13%. Other authors reported a 72.9% of Chagas' disease prevalence in amerindians settled in the Chaco since 1930-1940.

Phlebotomine sandfly species in Paraguay and their infection with Leishmania.

Nine species of sandflies, Lutzomyia (Nyssomyia) whitmani (Antunes and Countinho), Lutzomyia (Nyssomyia) intermedia (Lutz and Neiva), Lutzomyia (Psathyromyia) shannoni (Dyar), Lutzomyia migonei (Franca), Lutzomyia (Pintomyia) fischeri (Pinto), Lutzomyia (Pintomyia) pessoai (Countinho and Barretto), Lutzomyia cortelezzii (Brethes), Lutzomyia walkeri (Newstead) and Lutzomyia (Trichopygomyia) longispinus (Mangabeira), were caught, by human bait and Shannon trap, in four areas of Paraguay hyper-endemic for human leishmaniasis. Lutzomyia whitmani and L. intermedia were the predominant species. All the species collected were found to be anthropophilic. Hindgut infections with leishmanial promastigotes were observed in only one (0.38%) of the 266 L. whitmani dissected. No L. intermedia were found infected, giving an overall infection rate of one (0.16%) of 615 flies dissected. The results indicate a very low rate of natural infection in endemic areas of Paraguay.