Synthesis, activity, and molecular modeling studies of 1,2,3‐triazole derivatives from natural phenylpropanoids as new trypanocidal agents
| Autor: | Danielle Ferreira Dias, Ivo Santana Caldas, Camila Coelho Rodrigues, Fávero Reisdorfer Paula, Diogo Teixeira Carvalho, Thiago Belarmino de Souza |
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| Rok vydání: | 2019 |
| Předmět: |
1
2 3-Triazole Molecular model Trypanosoma cruzi Protozoan Proteins Triazole Cysteine Proteinase Inhibitors 01 natural sciences Biochemistry Mice Structure-Activity Relationship chemistry.chemical_compound In vivo parasitic diseases Drug Discovery Animals Humans Chagas Disease Trypanocidal agent Pharmacology Biological Products Molecular Structure biology 010405 organic chemistry Organic Chemistry Triazoles biology.organism_classification Trypanocidal Agents In vitro 0104 chemical sciences Molecular Docking Simulation Eugenol Cysteine Endopeptidases Disease Models Animal 010404 medicinal & biomolecular chemistry chemistry Drug Design Molecular Medicine |
| Zdroj: | Chemical Biology & Drug Design. 95:124-129 |
| ISSN: | 1747-0285 1747-0277 |
| DOI: | 10.1111/cbdd.13628 |
| Popis: | The search for compounds with new structural scaffolds is an important tool to the discovery of new drugs against Chagas disease. We report herein the synthesis of 1,2,3-triazoles obtained from eugenol and di-hydroeugenol and their in vitro and in vivo trypanocidal activity. These derivatives were obtained by a three-step objective route and were suitably characterized by 1 H and 13 C nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry. Two compounds (9 and 10) showed activity against epimastigote forms of Trypanosoma cruzi (Y strain) in the range 42.8-88.4 μM and were weakly toxic to cardiomyoblast cells (H9c2 cells). The triazole 10 was the most active derivative and could reduce more than 50% of parasitemia after a 100-mg/kg oral treatment of mice infected with T. cruzi. Molecular docking studies suggested this compound could act as a trypanocidal agent by inhibiting cruzain, an essential enzyme for T. cruzi metabolism, usually inhibited by triazole compounds. |
| Databáze: | OpenAIRE |
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