Navegando por Palavras-chave "Leishmanicidal"
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- ItemAcesso aberto (Open Access)Desenvolvimento de potenciais agentes leishmanicidas: benzotiazois inibidores de N-miristoiltransferase(Universidade Federal de São Paulo, 2016-06-17) Junqueira, Luis Otavio [UNIFESP]; Rando, Daniela Gonçales Galasse [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)N-myristoyltransferase is an enzyme responsible for anchoring proteins to the plasma mem- brane through a cotranslational mechanism of lipidation of proteins in eukaryotes. Previous studies have shown the benzothiazolic nucleus as promising for the development of a new class of NMT in- hibitor compounds. In this study, two benzothiazolic analogs were synthetized and tested against Leishmania (Leishmania) amazonensis. The study began with the synthesis of 6-hidroxi- benzotiazolato de etila followed by the alkylation of the 6-hidroxi position of this intermediate with a consecutive reaction of said alkylated intermediate with 3-picolamina or benzilamina. The products obtained had good purity despite the lower yield. It was also proposed the synthesis of a thiazolic de- rivative which would allow the valuation of the influence from the benzothiazolic core flexibility over the leishmanicide biological activity. The compound derived from 3-picolylamine was sent, along with its synthetic intermediates, for biological activity, showing activity in the order of 21,75 µM. The bio- logical activity profile was attributed to the low lipophilicity of the product obtained after the addition of the picolylaminic groups to the structure. The biological analysis of the derivate obtained from the benzylamine might confirm this hypothesis since it is more lipophilic than the 3-picolilamine derivate. Still, the activity shown by the tested compound demonstrates how this class of benzoheterocycles compounds might be promising for the development of new drugs with leishmanicide activity. Theo- retical studies using molecular docking were conducted with LmNMT in the means of assessing the binding of the benzothiazolic compounds that were obtained to this enzyme. The results showed that the benzothiazolic compounds constitute a class of molecules with a potential for interaction with the LmNMT target. The synthesis of flexible thiazolic analogs and finishing up of biological tests consti- tute the perspectives of the present study.
- ItemSomente MetadadadosGibbilimbol analogues as antiparasitic agents-Synthesis and biological activity against Trypanosoma cruzi and Leishmania (L.) infantum(Pergamon-Elsevier Science Ltd, 2016) Varela, Marina T. [UNIFESP]; Dias, Roberto Z. [UNIFESP]; Martins, Ligia F.; Ferreira, Daiane D.; Tempone, Andre G.; Ueno, Anderson K. [UNIFESP]; Lago, Joao Henrique G. [UNIFESP]; Fernandes, Joao Paulo S. [UNIFESP]The essential oils from leaves of Piper malacophyllum (Piperaceae) showed to be mainly composed by two alkenylphenol derivatives: gibbilimbols A and B. After isolation and structural characterization by NMR and MS data analysis, both compounds were evaluated against promastigote/amastigote forms of Leishmania (L.) infantum as well as trypomastigote/amastigote forms of Trypanosoma cruzi. The obtained results indicated that gibbilimbol B displayed potential against the tested parasites and low toxicity to mammalian cells, stimulating the preparation of several quite simple synthetic analogues in order to improve its activity and to explore the preliminary structure-activity relationships (SAR) data. Among the prepared derivatives, compound LINS03003 (n-octyl-4-hydroxybenzylamine) displayed the most potent IC50 values of 5.5 and 1.8 mu M against amastigotes of T. cruzi and L. (L.) infantum, respectively, indicating higher activity than the natural prototype. In addition, this compound showed remarkable selectivity index (SI) towards the intracellular forms of Leishmania (SI = 13.1) and T. cruzi (SI = 4.3). Therefore, this work indicated that preparation of synthetic compounds structurally based in the bioactive natural products could be an interesting source of novel and selective compounds against these protozoan parasites. (C) 2016 Elsevier Ltd. All rights reserved.
- ItemSomente MetadadadosLeishmanicidal activity of benzophenones and extracts from Garcinia brasiliensis Mart. fruits(Elsevier B.V., 2010-04-01) Pereira, I. O.; Marques, M. J.; Pavan, A. L. R.; Codonho, B. S.; Barbieri, C. L. [UNIFESP]; Beijo, L. A.; Doriguetto, A. C.; D'Martin, E. C.; Santos, M. H. dos; Universidade Federal de São Paulo (UNIFESP)Infections by protozoans of the genus Leishmania are the major worldwide health problem, with high endemicity in developing countries. the drugs of choice for the treatment of leishmaniasis are the pentavalent antimonials, which exert renal and cardiac toxicity. Thus, there is a strong need for safer and more effective treatments against leishmaniasis. the present study was designated to evaluate, by a bioguided assay, the leishmanicidal activity of extracts (hexane, ethyl-acetate and ethanolic) and molecules both obtained by means of extraction from pericarps of Garcinia brasiliensis fruits. the hexane extract presented the best activity on the extracellular (promastigotes) and intracellular (amastigotes) forms of Leishmania (L.) amazonensis, when compared to the other extracts. Based on these findings, this extract was fractionated by silica gel column chromatography, affording nine fractions then resulting in three purified prenylated benzophenones - 7-epi-clusianone (1), garciniaphenone (2) and guttiferone-a (3). They showed significant activity on Leishmania (L) amazonensis, and little toxicity for mammalian cells. Structure-activity relationships were evaluated showing that the IC(50) value displayed is dependent of prenyl groups and phenolic hydroxyls number, and inversely proportional to the hydrophobicity. Our results are promising, showing that these compounds are biologically active on Leishmania (L) amazonensis. (C) 2009 Elsevier GmbH. All rights reserved.