Computer‐Guided Trypanocidal Activity of Natural Lactones Produced by Endophytic Fungus of Euphorbia umbellata

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 (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.

In Vitro Biological Activity of Natural Products from the Endophytic Fungus Paraboeremia selaginellae against Toxoplasma gondii

“…Different stereoisomers of phomalactone ( F ) were isolated and reported previously from various sources [ 15 , 16 , 17 , 18 ], and some papers did not specify the absolute configuration [ 19 , 20 ], while others assigned the (5 R ,6 R ) absolute configuration to the large positive specific rotation [ 21 ], which was opposite to previous studies [ 15 , 16 , 17 , 18 , 22 ]. In order to determine the absolute configuration of phomalactone independently and unambiguously, we performed TDDFT-ECD, TDDFT-OR, and DFT-VCD studies, which consistently confirmed the (+)- cis -(5 S ,6 S ) absolute configuration (see Supplementary Materials ) [ 23 , 24 ].…”

Endophytic Fungi: An Effective Alternative Source of Plant-Derived Bioactive Compounds for Pharmacological Studies

“…(+)-phomalactone 186 (Figure 13), hydroxypestalopyrone 187 (Figure 13), and pestalopyrone 188 (Figure 13) were isolated from the endophytic fungus Aspergillus pseudonomiae J1 cultures and evaluated for in vitro anti-trypanosomal activity against the Trypanosoma cruzi Y strain using an anti-epimastigote assay. Compounds 186-188 showed moderate to weak anti-trypanosomal activities, with IC 50 values of 0.86 µM, 88.33 µM, and 580.19 µM, respectively [99].…”

Secondary Metabolites from Fungi — Honour of Prof. Dr. Ji-Kai Liu's 60th Birthday

“…Brassicicenes Q-X 51-58 have been isolated from the phytopathogenic fungus Alternaria brassicicola [99]. Brassicicene S 53 was found to show significant anti-inflammatory activity against the production of NO, TNF-α, and IL-1β at 10 μM.…”

“…A new irlactane-type, irlactin K 255, was isolated from the fermentation broth of the medicinal fungus Irpex lacteus [99]. The absolute configuration of 255 was established by single-crystal X-ray diffraction analysis.…”

“…Twenty-two tremulanes, irlactins F-J 261-265, L-M 266-267, irlactam A 268, and irpexolactins A-N 269-282, were isolated from cultures of the medicinal fungus Irpex lacteus [99,[103][104][105]. Irlactin I 264 exhibited moderate cytotoxicities on HL-60, SMMC-7721, A-549, MCF-7, and SW480 cells with IC 50 values of 16.23, 20.40, 25.55, 19.05, and 18.58 µM, respectively [104].…”