RESUMEN
Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC50 values of 2.30 and 2.45â µM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A2A , but also higher binding selectivity to A2A receptors than to A1 and A3 receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A2A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A2A receptors.
Asunto(s)
Antagonistas del Receptor de Adenosina A2/farmacología , Antiparkinsonianos/farmacología , Aspergillus ochraceus/química , Receptor de Adenosina A2A/metabolismo , Antagonistas del Receptor de Adenosina A2/química , Antagonistas del Receptor de Adenosina A2/metabolismo , Antagonistas del Receptor de Adenosina A2/farmacocinética , Animales , Antiparkinsonianos/química , Antiparkinsonianos/metabolismo , Antiparkinsonianos/farmacocinética , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Femenino , Humanos , Masculino , Ratones , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacocinética , Fármacos Neuroprotectores/farmacología , Ratas , EstereoisomerismoRESUMEN
Hyperjaponol H (1), a new filicinic acid-based meroterpenoid, with a 6/6/10 ring system trans-fused by hetero-Diels-Alder cycloaddition between a germacrane sesquiterpenoid and a filicinic acid moiety, was isolated from aerial parts of Hypericum japonicum. The elucidation of its structure and absolute configuration were accomplished by the analyses of extensive spectroscopic data and the comparison of Cotton effects of electron circular dichroism (ECD) with previously reported ones. The bioactivity assay showed that hyperjaponol H exhibited a moderate inhibitory efficacy on lytic Epstein-Barr virus (EBV) DNA replication in B95-8 cells.