Structural design, synthesis, and anti-Trypanosomatidae profile of new Pyridyl-thiazolidinones.

Autor: Conceição JMD; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil., Santos ACDS; Laboratory of Immunopathology and Molecular Biology, Department of Immunology, Aggeu Magalhães Institute, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil., Brayner FA; Laboratory of Immunopathology and Molecular Biology, Department of Immunology, Aggeu Magalhães Institute, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil; Instituto Keizo Asami (iLIKA), Campus UFPE, 50670-901, Recife, PE, Brazil., Alves LC; Laboratory of Immunopathology and Molecular Biology, Department of Immunology, Aggeu Magalhães Institute, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil; Instituto Keizo Asami (iLIKA), Campus UFPE, 50670-901, Recife, PE, Brazil., Pinto AF; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil., Brondani GL; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil., Oliveira Filho GB; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil., Bedor DCG; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil., Silva JWVD; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil., Sales Junior PA; Laboratory of Immunopathology and Molecular Biology, Department of Immunology, Aggeu Magalhães Institute, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil., Cavalcante MKA; Laboratory of Immunopathology and Molecular Biology, Department of Immunology, Aggeu Magalhães Institute, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil., Silva EDD; Instituto de Saúde e Biotecnologia, Universidade Federal do Amazonas, 69460-000, Coari, AM, Brazil., Pereira VRA; Laboratory of Immunopathology and Molecular Biology, Department of Immunology, Aggeu Magalhães Institute, Fundação Oswaldo Cruz, 50670-420, Recife, PE, Brazil., Leite ACL; Laboratory of Planning in Medicinal Chemistry, Department of Pharmaceutical Sciences, Center for Health Sciences, Federal University of Pernambuco, 50740-535, Recife, PE, Brazil. Electronic address: ana.lleite@ufpe.br.
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2023 Jun 05; Vol. 254, pp. 115310. Date of Electronic Publication: 2023 Apr 06.
DOI: 10.1016/j.ejmech.2023.115310
Abstrakt: The present work reports the synthesis of a novel series of pyridine-thiazolidinones with anti-Trypanosoma cruzi and leishmanicidal activities (compounds 10-27), derived from 2 or 4-pyridine thiosemicarbazones (1-9). The in vitro assays were performed with Trypanosoma cruzi trypomastigotes and amastigotes, as well as with Leishmania amazonensis promastigotes and amastigotes. The cytotoxicity profile was evaluated using the cell line RAW 264.7. From the 18 pyridine-thiazolidinones, 5 were able to inhibit trypomastigotes. Overall, all compounds inhibited amastigotes, highlighting compounds 15 (0.60 μM), 18 (0.64 μM), 17 (0.81 μM), and 27 (0.89 μM). Compounds 15 and 18 were able to induce parasite cell death through necrosis induction. Analysis by scanning electron microscopy showed that T. cruzi trypomastigotes treated with compounds 15 and 18 induced morphological changes such as shortening, retraction and curvature of the parasite body and leakage of internal content. Regarding the antiparasitic evaluation against Leishmania amazonensis, only compound 27 had a higher selectivity compared to Miltefosine against the amastigote form (IC 50  = 5.70 μM). Our results showed that compound 27 presented an antiparasitic activity for both Trypanosoma cruzi and Leishmania amazonensis. After in silico evaluation, it was suggested that the new pyridine-thiazolidinones had an appropriate drug-likeness profile. Our results pointed out a new chemical frame with an anti-Trypanosomatidae profile. The pyridine-thiazolidinones presented here for the first time could be used as a starting point for the development of new antiparasitic agents.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: