2-(phenylthio)ethylidene derivatives as anti-Trypanosoma cruzi compounds: Structural design, synthesis and antiparasitic activity
| Autor: | Rafaela Salgado Ferreira, José Wanderlan Pontes Espíndola, Diogo Rodrigo Magalhães Moreira, Marcos Veríssimo de Oliveira Cardoso, Maria Carolina Accioly Brelaz de Castro, Lucianna Rabelo Pessoa de Siqueira, Andresa Pereira de Oliveira Mendes, Ana Cristina Lima Leite, Cássio Santana Meira, Filipe Silva Villela, Elany Barbosa da Silva, Gevanio Bezerra de Oliveira Filho, Milena Botelho Pereira Soares, Valéria Rêgo Alves Pereira, Francielly Morais Rodrigues da Costa |
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| Rok vydání: | 2019 |
| Předmět: |
Chagas disease
Thiosemicarbazones Programmed cell death Antiparasitic medicine.drug_class Trypanosoma cruzi Pharmacology 01 natural sciences 03 medical and health sciences Structure-Activity Relationship Parasitic Sensitivity Tests Drug Discovery medicine Cytotoxic T cell Nifurtimox 030304 developmental biology 0303 health sciences biology Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry General Medicine medicine.disease biology.organism_classification Trypanocidal Agents 0104 chemical sciences Thiazoles Apoptosis Benznidazole Drug Design medicine.drug |
| Zdroj: | European journal of medicinal chemistry. 180 |
| ISSN: | 1768-3254 |
| Popis: | Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi . The current chemotherapy is based on benznidazole, and, in some countries, Nifurtimox, which is effective in the acute phase of the disease, but its efficacy in the chronic phase remains controversial. It can also cause serious side effects that lead sufferers to abandon treatment. In the present work, is reported the synthesis and trypanocidal activity of new 2-(phenylthio)ethylidene thiosemicarbazones ( 4 - 15 ) and 1,3-thiazoles ( 16 – 26 ). The cyclization of thiosemicarbazones into 1,3-thiazoles presents an improvement in the cytotoxic profile for T. cruzi parasite, denoting selective compounds. Compound 18 was identified as the most promising of all compounds tested, showing an IC 50 of 2.6 μM for the trypomastigote form and a non-cytotoxic effect on mouse spleen cells, reaching a selective index of 95.1. Among the 22 compounds tested, six compounds present a better trypanocidal activity, and five compounds have an equipotent activity compared to benznidazole. Flow cytometry and ultrastructural analysis were performed and indicate that compound 18 causes parasite cell death through apoptosis and acts via an autophagic pathway. |
| Databáze: | OpenAIRE |
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