Trypanocidal activity of new 1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine derivatives: synthesis, in vitro and in vivo studies
| Autor: | Gisele Bulhões Portapilla, Luiza R.S. Dias, Júlio C. A. V. Soares, Estela M.F. Muri, Camilo Henrique da Silva Lima, Maiara Voltarelli Providello, Sérgio de Albuquerque, Joana Lucius de Sousa Ribeiro |
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| Rok vydání: | 2021 |
| Předmět: |
Chagas disease
Male Stereochemistry Cell Survival Pyridines Trypanosoma cruzi Clinical Biochemistry COMPOSTOS HETEROCÍCLICOS Pharmaceutical Science Carbohydrazide 01 natural sciences Biochemistry Cell Line chemistry.chemical_compound Mice Structure-Activity Relationship Parasitic Sensitivity Tests In vivo Drug Discovery Pyridine medicine Moiety Animals Chagas Disease Amastigote Molecular Biology Trypanocidal agent Mice Inbred BALB C Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Chemistry Organic Chemistry medicine.disease Trypanocidal Agents In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry Molecular Medicine Pyrazoles |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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