Alba Inchausti

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.

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.

Leishmanicidal and Trypanocidal Activities of Acetogenins Isolated from Annona glauca

The dichloromethane extract of seeds of Annona glauca (Annonaceae) was active against three strains of Leishmania species. Nine known acetogenins were isolated and identified and then evaluated in vitro against Leishmania species and the bloodstream forms of Trypanosoma cruzi. Annonacin A and goniothalamicin showed activity against Leishmania, and glaucanisin, squamocin, annonacin A and annonacin against Trypanosoma cruzi reducing the parasites by 78%, 67%, 71% and 85%, respectively. Copyright

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.

Leishmanicidal and trypanocidal activity of extracts and secondary metabolites from basidiomycetes

Seventeen extracts and seven secondary metabolites isolated from basidiomycetes were tested in medium culture against promastigote forms of Leishmania spp. and bloodstream forms of Trypanosoma cruzi. Extracts from the culture filtrate or mycelium were generally inactive against the parasites except the Zucoagaricus genus mycelium extract which reduced by 47% the number of bloodstream forms. Striatin A, striatin B and podoscyphic acid exhibited in vitro activity at 10, 5 and 100 μg/mL, respectively. One compound showed activity against bloodstream forms of T. cruzi, the sesquiterpenoid naematolin, lysing the parasites by 79%. BALB/c mice infected with L. amazonensis were treated 3 weeks post‐infection with striatin A and striatin B by subcutaneous route for 15 days at 10 mg/kg daily. The reference drug, N‐methylglucamine antimonate, administered by subcutaneous injections at 28 mg Sbv/kg/day for 15 days reduced the parasite burden by 71.2% (p <0.05). Subcutaneous administration of straitin A at 10 mg/kg produced a weak decrease of the parasite burdens in the footpad by 17.6%. The treatment with striatin B had no effect and showed higher toxicity than striatin A.

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.

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.