Synthesis of quinolinyl chalcones and evaluation of their antimalarial activity.

Quinolinyl chalcones were synthesized and evaluated for their inhibition of the Plasmodium falciparum cystein protease falcipain and their activity against cultured P. falciparum parasites. They were also tested for in vivo efficacy in a rodent P. berghei model. Their activity against falcipain and as antimalarials was moderate, but antimalarial activity was probably not due to the inhibition of falcipain and may follow a different mechanism. 1-(2,4-Dichlorophenyl)-3-[3-(2-chloro-6,7-dimethoxiquinolinyl)]-2-propen-1-one 3j was the most promising compound among those here reported (IC50 19.0 microM).

Synthesis of pyridopyrimidone derivatives and their activity against P. falciparum in vitro.

Pyridopyrimidone derivatives 4a-d and 5a- were synthesized as potential antimalarial agents on the basis of the pharmacological properties of existing quinolone analogues such as ciprofloxacine IC50 39.8 microM. Meanwhile among these new compounds, only the 3-amino-7-methyl-1(H)pyrazolo[3,4-b]-pyrido [1,2: 1'2']pyrimido-4-ona 4b, produces significant antimalarial activity IC50 0.42 microM against P. falciparum in vitro. The remaining compounds were effective as antimalarial agents leading from IC50 1.0 microM to IC50 4.47 microM.

Synthesis and activity of some quinolone derivatives against Plasmodium falciparum in vitro.

Quinolones 7a-i and 8a-i were synthesized and tested in vitro as antimalarial against Plasmodium falciparum in chloroquine resistant strain. The above compounds were inactive at concentrations of 1.0 x 10(-4) M except the quinolone 3-amino-9-(2,4-dichlorophenyl)-1H-pyrazolo[3,4-b]-4-quinolone 7h which showed IC50 of 5.06 microM given the most interesting results.

Plasmodium falciparum: surface modifications of infected erythrocytes from clinical isolates. Evidence of antigenic diversity using Venezuelan human malarial sera.

Infections of human erythrocytes with the mature asexual blood stages of Plasmodium falciparum result in antigenic changes in the host cell membrane that, by virtue of their position, length of exposure, and close association with functional changes critical to pathogenesis, are a potential important target for host effector mechanisms. These parasite-induced antigens expressed on the surface of infected erythrocytes have been shown to exhibit considerable polymorphism. An antibody-mediated agglutination assay using malaria serum samples from different regions of Venezuela has been developed to examine the extent of antigenic diversity of infected red blood cells (IRBC) taken from subjects with naturally acquired P. falciparum infections. An important humoral immune recognition of surface molecules from red blood cells infected with a wide variety of clinical isolates of P. falciparum was observed even when sera from individuals experiencing a single episode of malaria were used. A process of in vivo antigenic variation of surface molecules is postulated, since agglutination of IRBC was observed with acute heterologous but not autologous sera. When sera obtained from Amerindians inhabiting the Venezuelan Amazon were assayed, a strong immune response to different parasite isolates, including those of another geographic region, was observed, suggesting the recognition of highly conserved immunogenic parasitic epitopes in people exposed to multiple malaria infections.

Detection of antibodies to a 70 kDa Plasmodium falciparum exoantigen in malarious subjects using synthetic peptides.

Indirect fluorescent antibody (IFA) tests and enzyme-linked immunosorbent assays (ELISA) were used to measure antibodies to Plasmodium falciparum in patients with acute malaria from Bolivar State, Venezuela. Antibody titers increased significantly with repeated malarial episodes. IgG antibody responses to 4 synthetic peptides (termed C2, C3, C5, C10) derived from a 70 kDa P. falciparum (Indochina I/CDC strain) exoantigen were evaluated by a peptide-ELISA with overall positivity rates of 20%, 40%, 20% and 58%, respectively. Seropositivity to peptide C10 was consistently over 50% (range 53-75%) among patients of different ages. Overall IgM reactivity to the respective peptides was 53%, 30%, 83% and 70%. IgM reactivity was generally greater in patients with primary malarial infections. The ELISA is a useful adjunct to the IFA in measuring naturally-occurring antibodies to specific parasite proteins.

Revision de la taxonomia del genero Leishmania y de los metodos empleados. / Review of the taxonomy of genus Leishmania and the methods used

Debido a las dificultades existentes en la actualidad para la clasificacion de los parasitos del genero Leishmania, dificultades que se agudizan para las poblaciones del Nuevo Mundo, se revisan y discuten los varios criterios taxonomicos utilizados hasta el presente para diferenciar los parasitos del genero. Estos criterios considerados e interpretados en conjunto puedem constituirse en una valiosa herramienta para la elucidacion de este interesante problema, tal como ha sido sugerido por Lumsden (28)

A new method for the partial purification of leishmania amastigotes from cutaneous lesionS.

Amastigotes from Leishmania braziliensis and L. mexicana were isolated from cutaneous lesions in infected animals using the plant lectin Concanavalin A as a specific agglutination agent. Amastigotes were collected in preparations of up to 95% purity as determined by cell count. The parasites obtained by this method showed no apparent loss of viability as measured by growth rated and DNA replication, or pathogenicity as measured by routine passages in hamsters or mice.