Title:	In vitro evaluation of 4-phenyl-5-(40-X-phenyl)-1,3,4-thiadiazolium-2- phenylaminide chlorides and 3[N-40-X-phenyl]-1,2,3-oxadiazolium-5- olate derivatives on nitric oxide synthase and arginase activities of Leishmania amazonensis
Authors:	Bezerra, Romulo J. Soares Leon, Leonor Laura Echevarria, Aurea Reis, Camila M. Silva, Liliane Gomes Agostinho, Carla G. Fernandes, Renan A. Cavalheiro, Marilene M. Canto Genestra, Marcelo S.
Affilliation:	Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. Universidade Federal Rural do Rio de Janeiro. Departamento de Química. Seropédica, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil.
Abstract:	Leishmaniasis is a spectrum of infectious diseases caused by Leishmania protozoan parasites. The purpose of this study was to perform, in vitro, a comparative analysis of the activity amastigotes. Results showed excellent efficacy of all compounds against axenic amastigotes, compared to pentamidine isethionate, the reference drug used. The cytotoxic effect of these mesoionic compounds of six mesoionic compounds (three 1,3,4-thiadiazolium-2-aminide and three 1,2,3-oxadiazolium-5-olate class compounds) was evaluated in mouse peritoneal macrophages using MTT assay, low toxicity ( 10%) for these mammalian cells being observed. In an attempt to define a potential drug target, the activities of nitric oxide synthase (NOS) and arginase of the parasites treated with the mesoionic derivatives were evaluated. NOS was purified from a cell-free extract of infective promastigotes and axenic amastigotes and all derivatives tested were able to inhibit the enzyme as monitored by the decrease of NADPH consumption. Arginase activity from both stages of the parasite was measured using urea production and none of the compounds inhibited the enzyme activity of axenic amastigotes. On the other hand, when tested with promastigotes, those compounds without and substituents inhibited arginase activity.
Keywords:	Leishmania amazonensis Promastigote Axenic amastigote Mesoionic compounds Nitric oxide synthase Arginase
DeCS:	Leishmania amazonensis Arginase Nitric oxide synthase
Issue Date:	2013
Publisher:	Elsevier
Citation:	BEZERRA, Romulo J. Soares; et al. In vitro evaluation of 4-phenyl-5-(40-X-phenyl)-1,3,4-thiadiazolium-2- phenylaminide chlorides and 3[N-40-X-phenyl]-1,2,3-oxadiazolium-5- olate derivatives on nitric oxide synthase and arginase activities of Leishmania amazonensis. Experimental Parasitology, v.135, n.1, p. 50–54, 2013.
DOI:	10.1016/j.exppara.2013.05.008
ISSN:	0014-4894
Copyright:	restricted access
Appears in Collections:	IOC - Artigos de Periódicos

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