Computer‐Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of Euphorbia umbellata. Issue 10 (7th September 2021)

• Record Type: Journal Article
• Authors: Gusmão, Amanda Santos; Abreu, Lucas Silva; Tavares, Josean Fechine; de Freitas, Humberto Fonseca; Silva da Rocha Pita, Samuel; dos Santos, Elda Gonçalves; Caldas, Ivo Santana; Vieira, André Alexandre; Silva, Eliane Oliveira
• Is Part Of: Chemistry & biodiversity. Volume 18:Issue 10(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-07
• Subjects: Aspergillus pseudonomiae -- endophytic fungus -- pyrone -- molecular modeling -- Trypanosoma cruzi; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.202100493
• Languages: English
• ISSNs: 1612-1872

Abstract

Abstract: 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 ( Tc GAPDH) inhibition, and the binding free energy for all three Tc GAPDH‐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. Abstract :