ABSTRACT
Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.
Subject(s)
Antiparasitic Agents/pharmacology , Kinetoplastida/drug effects , Kinetoplastida/pathogenicity , Neglected Diseases/drug therapy , Neglected Diseases/parasitology , Nitrogen Compounds/pharmacology , Polyamines/pharmacology , Antiparasitic Agents/chemistry , Leishmania/drug effects , Molecular Structure , Nitrogen Compounds/chemistry , Parasitic Sensitivity Tests , Polyamines/chemistry , Trypanosoma/drug effectsABSTRACT
Trypanosome infections have been reported in several species of fish, in majority of cases described on the basis of morphological characteristics. Trypanosomes in fish are heteroxenous and transmitted by hirudineans. This study aims to evaluate the prevalence and density of infections by Trypanosoma sp. in blood from three species of catfish, Hypostomus regani, H. strigaticeps, H. albopunctatus, from the Mogi Guaçu River, Pirassununga, São Paulo, Brazil. Further, this study intends to characterize the Trypanosoma specimens found in the blood of these fish by morphological and molecular techniques. The trypanosomes overall prevalence observed was 47.6% with a general average density of 0.75 parasites/µl of blood. Hypostomus regani and Hypostomus strigaticeps showed a significant difference in prevalence. The average densities of parasites were not significantly different among the three fish species. Similar findings were observed for the monthly variations in densities. The parasites found in the three species of catfish studied showed similar morphological characteristics. The morphological data and the statistical analyses used in this study didnt show the formation of groups. The analyses provided evidence of the presence of pleomorphisms in the trypanosomes found in the three studied fish.(AU)
Infecções por tripanossomas foram descritas em diversas espécies de peixes, sendo a maioria das descrições baseada nas características morfológicas. Tripanossomas de peixes são heteroxenos e transmitidos por hirudíneos. Este estudo tem como objetivo a avaliação da prevalência e densidade da infecção por Trypanosoma sp. no sangue de três espécies de cascudos, Hypostomus regani, H.strigaticeps, H.albopunctatus, do Rio Mogi-Guaçu, Pirassununga, São Paulo, Brasil. Além disso, pretende-se a caracterização das espécies de Trypanosoma encontradas no sangue desses peixes, por meio da utilização de técnicas morfólogicas e moleculares. A prevalência total de tripanossomas foi de 47,6%, e a densidade média foi de 0,75 parasitas/ µl de sangue. Hypostomus regani e Hypostomus strigaticeps apresentaram diferenças significativas em prevalência. As médias das densidades dos parasitas não apresentaram diferenças significativas entre as três espécies de peixes estudadas. O mesmo foi observado com a variação mensal das densidades. Os parasitas encontrados nas três espécies de cascudo possuíam características morfológicas semelhantes. As análises morfológicas e estatísticas obtidas neste estudo não mostraram a formação de grupos. As análises evidenciaram a presença de pleomorfismo dos tripanossomas encontrados nas três espécies de peixes estudados.(AU)