Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluations-Reference-Cited by-同舟云学术

Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluations

Published:2023-08 Issue:16 Volume:15 Page:1469-1489
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Vieira da Silva Torchelsen Fernanda Karoline¹^ORCID,Fernandes Pedrosa Tamiles Caroline²^ORCID,Rodrigues Michelle Peixoto³^ORCID,de Aguiar Alex Ramos³,de Oliveira Fabrício Marques⁴^ORCID,Amarante Giovanni Wilson⁵^ORCID,Sales-Junior Policarpo Ademar⁶^ORCID,Branquinho Renata Tupinambá¹^ORCID,Gomes da Silva Sirlaine Pio⁷,Talvani André²⁷^ORCID,Fonseca Murta Silvane Maria⁶^ORCID,Martins Felipe Terra⁸,Braun Rodrigo Ligabue⁹^ORCID,Teixeira Róbson Ricardo³^ORCID,Furtado Mosqueira Vanessa Carla¹^ORCID,Lana Marta de¹²^ORCID

Affiliation:

1. Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, 35400-000, Brazil

2. Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, 35400-000, Brazil

3. Departamento de Química, Universidade Federal de Viçosa, Viçosa, Minas Gerais, 30130-171, Brazil

4. Instituto Federal de Educação de Minas Gerais, Ouro Branco, Minas Gerais, 36420-000, Brazil

5. Departamento de Química, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, 36036-900, Brazil

6. Centro de Pesquisas René-Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, 30190-009, Brazil

7. Programa de pós-graduação em Saúde e Nutrição, Escola de Nutrição, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, 35400-000, Brazil

8. Departamento de Química, Universidade Federal de Goiás, Goiânia, Goiás, 74001-970, Brazil

9. Departamento de Ciências Farmacêuticas, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Rio Grande do Sul, 90050-170, Brazil

Abstract

Background: Chagas disease is a life-threatening illness caused by Trypanosoma cruzi. The involvement of serine-/arginine-rich protein kinase in the T. cruzi life cycle is significant. Aims: To synthesize, characterize and evaluate the trypanocidal activity of diamides inspired by kinase inhibitor, SRPIN340. Material & Methods: Synthesis using a three-step process and characterization by infrared, nuclear magnetic resonance and high-resolution mass spectrometry were conducted. The selectivity index was obtained by the ratio of CC50/IC50 in two in vitro models. The most active compound, 3j, was evaluated using in vitro cytokine assays and assessing in vivo trypanocidal activity. Results: 3j activity in the macrophage J774 lineage showed an anti-inflammatory profile, and mice showed significantly reduced parasitemia and morbidity at low compound dosages. Conclusion: Novel diamide is active against T. cruzi in vitro and in vivo.

Funder

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Financiadora de Estudos e Projetos

Fundação de Amparo à Pesquisa do Estado de Minas Gerais

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

https://www.future-science.com/doi/pdf/10.4155/fmc-2023-0090

Reference86 articles.

1. Nova tripanozomiaze humana: estudos sobre a morfolojia e o ciclo evolutivo do Schizotrypanum cruzi n. gen., n. sp., ajente etiolojico de nova entidade morbida do homem

2. WHO. Chagas disease (American trypanosomiasis). (2021). www.who.int/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis) (Accessed 13 April 2022).

3. Pan American Health Organization. Chagas in the Americas for public health workers (2022). www.paho.org/en/documents/factsheet-chagas-disease-americas-public-health-workers (Accessed 10 January 2023).

4. Chagas disease: A Latin American health problem becoming a world health problem

5. Challenges in the management of Chagas disease in Latin-American migrants in Europe