Computer‐Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of Euphorbia umbellata
| Autor: | Samuel Silva da Rocha Pita, Elda Gonçalves dos Santos, André A. Vieira, Ivo Santana Caldas, Lucas Silva Abreu, Eliane de Oliveira Silva, Amanda Santos Gusmão, Josean Fechine Tavares, Humberto Fonseca de Freitas |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Trypanosoma cruzi In silico Bioengineering Dehydrogenase Biochemistry Plant use of endophytic fungi in defense Microbiology Lactones chemistry.chemical_compound Parasitic Sensitivity Tests Euphorbia medicine Bioassay Molecular Biology IC50 Phylogeny Biological Products Molecular Structure biology General Chemistry General Medicine biology.organism_classification Trypanocidal Agents Pyrone chemistry Benznidazole Molecular Medicine medicine.drug |
| Zdroj: | Chemistry & Biodiversity. 18 |
| ISSN: | 1612-1880 1612-1872 |
| DOI: | 10.1002/cbdv.202100493 |
| Popis: | Hundreds of millions of people worldwide are affected by Chagas' disease caused by Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were in silico evaluated for rational guidance of their bioassay screening. All lactones displayed in vitro activity against T. cruzi epimastigote and trypomastigote forms. Notably, the IC50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to T. cruzi glyceraldehyde-3-phosphate dehydrogenase (TcGAPDH) inhibition, and the binding free energy for all three TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (-3.38), corroborating with IC50 assays. These results highlight the potential of these lactones for further anti-T. cruzi drug development. |
| Databáze: | OpenAIRE |
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