In vitro evaluation of cytotoxicity and leishmanicidal activity of phthalimido-thiazole derivatives.

Autor: Aliança ASDS; Laboratório de Imunologia Keizo Asami-LIKA/UFPE and Laboratório de Biologia Celular e Molecular, Centro de Pesquisas Aggeu Magalhães/Fundação Oswaldo Cruz-CPqAM/FIOCRUZ, Recife, PE CEP: 50670-420, Brazil; Post Graduate Program in Tropical Medicine (UFPE), Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife, PE CEP: 50670-901, Brazil., Oliveira AR; Laboratório de Planejamento em Química Medicinal, Departamento de Ciências Farmacêuticas, Post Graduate Program in Pharmaceutical Sciences (UFPE), Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE CEP: 50740-520, Brazil. Electronic address: arsenio3000@hotmail.com., Feitosa APS; Laboratório de Imunologia Keizo Asami-LIKA/UFPE and Laboratório de Biologia Celular e Molecular, Centro de Pesquisas Aggeu Magalhães/Fundação Oswaldo Cruz-CPqAM/FIOCRUZ, Recife, PE CEP: 50670-420, Brazil., Ribeiro KRC; Laboratório de Imunologia Keizo Asami-LIKA/UFPE and Laboratório de Biologia Celular e Molecular, Centro de Pesquisas Aggeu Magalhães/Fundação Oswaldo Cruz-CPqAM/FIOCRUZ, Recife, PE CEP: 50670-420, Brazil., de Castro MCAB; Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães/Fundação Oswaldo Cruz-CPqAM/FIOCRUZ, Recife, PE CEP: 50670-420, Brazil; Laboratório de Parasitologia, Universidade Federal de Pernambuco-CAV, Vitória de Santo Antão, PE CEP: 55608-680, Brazil., Leite ACL; Laboratório de Planejamento em Química Medicinal, Departamento de Ciências Farmacêuticas, Post Graduate Program in Pharmaceutical Sciences (UFPE), Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE CEP: 50740-520, Brazil., Alves LC; Laboratório de Imunologia Keizo Asami-LIKA/UFPE and Laboratório de Biologia Celular e Molecular, Centro de Pesquisas Aggeu Magalhães/Fundação Oswaldo Cruz-CPqAM/FIOCRUZ, Recife, PE CEP: 50670-420, Brazil., Brayner FA; Laboratório de Imunologia Keizo Asami-LIKA/UFPE and Laboratório de Biologia Celular e Molecular, Centro de Pesquisas Aggeu Magalhães/Fundação Oswaldo Cruz-CPqAM/FIOCRUZ, Recife, PE CEP: 50670-420, Brazil; Post Graduate Program in Tropical Medicine (UFPE), Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife, PE CEP: 50670-901, Brazil.
Jazyk: angličtina
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2017 Jul 15; Vol. 105, pp. 1-10. Date of Electronic Publication: 2017 May 04.
DOI: 10.1016/j.ejps.2017.05.005
Abstrakt: It is estimated that the worldwide prevalence of leishmaniasis is around 12 million individuals in 80 countries, with 400,000new cases per year. In the search for new leishmanicidal agents, the hybrid phthalimido-thiazoles have been identified as an important scaffold for drug design and discovery. The present study thus reports the in vitro activity of a series of phthalimido-thiazole derivatives. Cytotoxicity against a strain of L. infantum, Vero cells, J774 macrophages and peritoneal macrophages was evaluated, as well as nitric oxide (NO) production. Activity against amastigote and promastigote forms of L. infantum and microscopic changes in the parasite and intracellular targets of the parasite were achieved. The results show that the compounds arising from hybridization of phthalimide and 1,3-thiazole exhibit promising leishmanicidal activity. Compounds 2j and 2m were the most potent of the series tested and the parasites treated with these compounds exhibited ultrastructural changes, such as cell body shrinkage, loss of cellular membrane integrity, vacuolization of cytoplasm, membrane profiles surrounding organelles and swelling of mitochondria. The data showed that these compounds reduced the survival of intracellular amastigotes and presented low toxicity for mammalian cells. The compounds produced increased NO production compared to untreated cells in non-infected macrophages. Treated promastigote forms showed an increase in the number of cells stained with propidium iodide. The compounds brought about significant changes in mitochondrial membrane potential. According to the present study, phthalimido-thiazole compounds exhibit leishmanicidal activity and could be used to develop novel antileishmaniasis drugs and explore potential molecular targets.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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