Computer‐Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of <i>Euphorbia umbellata</i>
Amanda Santos Gusmão, Lucas Silva Abreu, Josean Fechine Tavares, Humberto Fonseca de Freitas, Samuel Silva da Rocha Pita, Elda Gonçalves dos Santos, Ivo Santana Caldas, André A. Vieira, Eliane de Oliveira Silva
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 IC 50 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 IC 50 assays. These results highlight the potential of these lactones for further anti‐ T. cruzi drug development.