Open AccessIn Vitro , In Silico , and In Vivo Analyses of Novel Aromatic Amidines against Trypanosoma cruzi
Author(s) -
Camila C. Santos,
Jessica Lionel,
Raiza Brandão Peres,
Marcos Meuser Batista,
Patrícia Bento da Silva,
Gabriel Melo de Oliveira,
Cristiane F. da Silva,
D. G. J. Batista,
Sandra Maria O. Souza,
Carolina Horta Andrade,
Bruno J. Neves,
Rodolpho C. Braga,
Donald A. Patrick,
Svetlana M. Bakunova,
Richard R. Tidwell,
Maria de Nazaré Correia Soeiro
Publication year - 2017
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.02205-17
Subject(s) - trypanosoma cruzi , in silico , in vivo , in vitro , chemistry , biology , stereochemistry , microbiology and biotechnology , biochemistry , genetics , parasite hosting , computer science , world wide web , gene
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.
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