Trypanocidal activity of new 1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine derivatives: Synthesis, in vitro and in vivo studies.

Autor: Ribeiro JLS; Universidade Federal Fluminense, Faculdade de Farmácia, Laboratório de Química Medicinal, RJ, Brazil., Soares JCAV; Universidade Federal Fluminense, Faculdade de Farmácia, Laboratório de Química Medicinal, RJ, Brazil., Portapilla GB; Universidade de São Paulo, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, SP, Brazil., Providello MV; Universidade de São Paulo, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, SP, Brazil., Lima CHS; Universidade Federal do Rio de Janeiro, Instituto de Química, RJ, Brazil., Muri EMF; Universidade Federal Fluminense, Faculdade de Farmácia, Laboratório de Química Medicinal, RJ, Brazil., de Albuquerque S; Universidade de São Paulo, Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, SP, Brazil. Electronic address: sdalbuqu@fcfrp.usp.br., Dias LRS; Universidade Federal Fluminense, Faculdade de Farmácia, Laboratório de Química Medicinal, RJ, Brazil. Electronic address: lrsdias@id.uff.br.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2021 Jan 01; Vol. 29, pp. 115855. Date of Electronic Publication: 2020 Nov 06.
DOI: 10.1016/j.bmc.2020.115855
Abstrakt: Despite the serious public health problems caused by Chagas disease in several countries, the available therapy remains with only two drugs that are poorly active during the chronic phase of the disease in addition to having severe side effects. In search of new trypanocidal agents, herein we describe the synthesis and biological evaluation of eleven new 1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine compounds containing the carbohydrazide or the 2,3-dihydro-1,3,4-oxadiazole moieties. Two of them showed promising in vitro activity against amastigote forms of T. cruzi and were evaluated in vivo in male BALB/c mice infected with T. cruzi Y strain. Our results suggest that the substitution at the C-2 position of the phenyl group connected to the carbohydrazide or to the 2,3-dihydro-1,3,4-oxadiazole moieties plays an important role in the trypanocidal activity of this class of compounds. Moreover, the compound containing the 2,3-dihydro-1,3,4-oxadiazole moiety has demonstrated more favorable structural requirements for in vivo activity than its carbohydrazide analog.
(Copyright © 2020. Published by Elsevier Ltd.)
Databáze: MEDLINE
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