Thiosemicarbazone and thiazole: in vitro evaluation of leishmanicidal and ultrastructural activity on Leishmania infantu
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Medicinal Chemistry Research https://doi.org/10.1007/s00044-020-02619-z
ORIGINAL RESEARCH
Thiosemicarbazone and thiazole: in vitro evaluation of leishmanicidal and ultrastructural activity on Leishmania infantum Camila Marques Queiroz 1,2 Gevanio Bezerra de Oliveira Filho3 José Wanderlan Pontes Espíndola3 Amanda Vasconcelos do Nascimento1 Amanda Silva dos Santos Aliança1 Virginia Maria Barros de Lorena4 Ana Paula Sampaio Feitosa1,5 Paula Roberta da Silva1 Luiz Carlos Alves1,5 Ana Cristina Lima Leite3 Fábio André Brayner1,2,5 ●
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Received: 8 June 2020 / Accepted: 21 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Leishmaniasis is a much-neglected tropical disease, especially in developing countries. Visceral Leishmaniasis (VL) is the most severe form of this infection caused by Leishmania infantum specie. It affects the splenic and hepatic systems and, when left untreated, it is fatal in 95% of cases. There is no human vaccine available and the recommended treatment not only presents adverse effects but it enables the development of resistant strains if interrupted. Hence, the urgent search for new leishmanicidal compounds. In the present work, we evaluated the in vitro leishmanicidal action of new thiosemicarbazone and thiazolidine compounds against the evolutionary forms of L. infantum, as well as their hemolytic activity, ultrastructural alterations, cytotoxicity, and nitric oxide levels on peritoneal macrophages. The inhibitory concentration 50% (IC50) against promastigote forms varied from 8.62 to 34.36 µM. In the evaluation of cytotoxicity, values of CC50 in peritoneal macrophages varied from 31.80 to 196.38 µM. Data showed that compounds JW-16.2 and GT-14 were the most promising in the series as they displayed the highest CC50 (184.58 and 196.38 μM), SI (19 and 15), low hemolytic activity, induced NO production in uninfected and infected macrophages and reduced survival of amastigotes (24.39 and 16.51 μM). Ultrastructural alterations, such as shrinkage of the cell body, shortening of the flagellum, and vacuolization of the cytoplasm, were identified. Promastigote forms treated with compounds GT-14 showed depolarization of mitochondria. Therefore, both compounds are promising due to low cytotoxicity to mammalian cells and leishmanicidal action. Keywords Visceral Leishmaniasis Thiosemicarbazone Thiazole L. infantum Amastigotes Ultrastructure ●
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Introduction
Supplementary information The online version of this article (https:// doi.org/10.1007/s00044-020-02619-z) contains supplementary material, which is available to authorized users. * Camila Marques Queiroz [email protected] 1
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Laboratório de Leishmaniose e Mutagênese, Departamento de Parasitologia, Instituto Aggeu Magalhães (IAM), Fundação Oswaldo Cruz (Fiocruz-Pernambuco), Av. Prof. Moraes Rego s/n – Cidade Universitária, Recife, PE 50670-420, Brazil Programa de Pós-Graduação em Medicina Tropical, Universidade Federal de Pernambuco (UFPE
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