In Vitro , In Silico , and In Vivo Analyses of Novel Aromatic Amidines against Trypanosoma cruzi-Reference-Cited by-同舟云学术

In Vitro , In Silico , and In Vivo Analyses of Novel Aromatic Amidines against Trypanosoma cruzi

Published:2018-02 Issue:2 Volume:62 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Santos Camila C.¹,Lionel Jéssica R.¹,Peres Raiza B.¹,Batista Marcos M.¹,da Silva Patrícia B.¹,de Oliveira Gabriel M.¹,da Silva Cristiane F.¹,Batista Denise G. J.¹,Souza Sandra Maria O.²,Andrade Carolina H.³,Neves Bruno J.³,Braga Rodolpho C.³,Patrick Donald A.⁴,Bakunova Svetlana M.⁴,Tidwell Richard R.⁴,Soeiro Maria de Nazaré C.¹

Affiliation:

1. Laboratory of Cellular Biology (LBC), Oswaldo Cruz Institute (Fiocruz), Rio de Janeiro, RJ, Brazil

2. Laboratory of Structural Biology (LBE), Oswaldo Cruz Institute (Fiocruz), Rio de Janeiro, RJ, Brazil

3. Laboratory for Molecular Modeling and Drug Design (LabMol), Faculdade de Farmácia, Universidade Federal de Goiás, Goiânia, Brazil

4. Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA

Abstract

ABSTRACT Five bis-arylimidamides were assayed as anti- Trypanosoma cruzi agents by in vitro , in silico , and in vivo approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested in vivo led to a 40% reduction in parasitemia (0.1 mg/kg of body weight/5 days intraperitoneally) but without mortality protection. In silico target fishing suggested DNA as the main target, but ultrastructural data did not match.

Funder

MCTI | Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.02205-17

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