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Effect of a thiohydantoin salt derived from l-Arginine on Leishmania amazonensis and infected cells: Insights from biological effects to molecular docking interactions.
da Silva Bortoleti, Bruna Taciane; Camargo, Priscila Goes; Gonçalves, Manoela Daiele; Tomiotto-Pellissier, Fernanda; Silva, Taylon Felipe; Concato, Virginia Marcia; Detoni, Mariana Barbosa; Bidóia, Danielle Larazin; da Silva Lima, Camilo Henrique; Rodrigues, Carlos Rangel; Bispo, Marcelle de Lima Ferreira; de Macedo, Fernando Cesar; Conchon-Costa, Ivete; Miranda-Sapla, Milena Menegazzo; Wowk, Pryscilla Fanini; Pavanelli, Wander Rogério.
Afiliação
  • da Silva Bortoleti BT; Biosciences and Biotechnology Postgraduate Program, Carlos Chagas Institute, (ICC/Fiocruz/PR), Curitiba, Paraná, Brazil; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • Camargo PG; Federal University of Rio de Janeiro, Faculty of Pharmacy, Rio de Janeiro, Rio de Janeiro, Brazil; State University of Londrina (UEL/PR), Chemistry Department, Londrina, Paraná, Brazil.
  • Gonçalves MD; State University of Londrina (UEL/PR), Laboratory of Biotransformation and Phytochemistry, Londrina, Paraná, Brazil.
  • Tomiotto-Pellissier F; Biosciences and Biotechnology Postgraduate Program, Carlos Chagas Institute, (ICC/Fiocruz/PR), Curitiba, Paraná, Brazil; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • Silva TF; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • Concato VM; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • Detoni MB; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • Bidóia DL; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • da Silva Lima CH; Federal University of Rio de Janeiro, Chemistry Institute, Rio de Janeiro, Rio de Janeiro, Brazil.
  • Rodrigues CR; Federal University of Rio de Janeiro, Faculty of Pharmacy, Rio de Janeiro, Rio de Janeiro, Brazil.
  • Bispo MLF; State University of Londrina (UEL/PR), Chemistry Department, Londrina, Paraná, Brazil.
  • de Macedo FC; State University of Londrina (UEL/PR), Chemistry Department, Londrina, Paraná, Brazil.
  • Conchon-Costa I; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil.
  • Miranda-Sapla MM; Federal University of Rio de Janeiro, Chemistry Institute, Rio de Janeiro, Rio de Janeiro, Brazil.
  • Wowk PF; Carlos Chagas Institute (ICC/Fiocruz/PR), Molecular Immunology and Cellular Group, Curitiba, Paraná, Brazil. Electronic address: pryscilla.wowk@fiocruz.br.
  • Pavanelli WR; State University of Londrina (UEL/PR), Laboratory of Immunoparasitology, Londrina, Paraná, Brazil. Electronic address: wanderpavanelli@uel.br.
Chem Biol Interact ; 403: 111216, 2024 Nov 01.
Article em En | MEDLINE | ID: mdl-39218371
ABSTRACT
Leishmaniasis is a neglected tropical disease caused by parasites of the genus Leishmania and is responsible for more than 1 million new cases and 70,000 deaths annually worldwide. Treatment has high costs, toxicity, complex and long administration time, several adverse effects, and drug-resistant strains, therefore new therapies are urgently needed. Synthetic compounds have been highlighted in the medicinal chemistry field as a strong option for drug development against different diseases. Organic salts (OS) have multiple biological activities, including activity against protozoa such as Leishmania spp. This study aimed to investigate the in vitro leishmanicidal activity and death mechanisms of a thiohydantoin salt derived from l-arginine (ThS) against Leishmania amazonensis. We observed that ThS treatment inhibited promastigote proliferation, increased ROS production, phosphatidylserine exposure and plasma membrane permeabilization, loss of mitochondrial membrane potential, lipid body accumulation, autophagic vacuole formation, cell cycle alteration, and morphological and ultrastructural changes, showing parasites death. Additionally, ThS presents low cytotoxicity in murine macrophages (J774A.1), human monocytes (THP-1), and sheep erythrocytes. ThS in vitro cell treatment reduced the percentage of infected macrophages and the number of amastigotes per macrophage by increasing ROS production and reducing TNF-α levels. These results highlight the potential of ThS among thiohydantoins, mainly related to the arginine portion, as a leishmanicidal drug for future drug strategies for leishmaniasis treatment. Notably, in silico investigation of key targets from L. amazonensis, revealed that a ThS compound from the l-arginine amino acid strongly interacts with arginase (ARG) and TNF-α converting enzyme (TACE), suggesting its potential as a Leishmania inhibitor.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arginina / Espécies Reativas de Oxigênio / Simulação de Acoplamento Molecular / Leishmania / Macrófagos Limite: Animals / Humans Idioma: En Revista: Chem Biol Interact Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Irlanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Arginina / Espécies Reativas de Oxigênio / Simulação de Acoplamento Molecular / Leishmania / Macrófagos Limite: Animals / Humans Idioma: En Revista: Chem Biol Interact Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Irlanda