Oxidative stress has been implicated in the etiology of Parkinson’s disease (PD). Molecules non-covalently binding to the Keap1–Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition.

Three novel 12,13-seco-spirocyclic polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives, named hyperilongenols A–C (1–3), were isolated from the stems and leaves of Hypericum longistylum Oliv. Their planar structures were established by a combination of 1D and 2D NMR, HRESIMS data, and chemical derivatization. Their absolute configurations were defined using electronic circular dichroism (ECD) spectroscopy and X-ray crystallography. Compounds 1–3 represent the first examples of naturally occurring 12,13-seco-spirocyclic PPAPs with an enolizable β,β′-tricarbonyl system. The O-methylation of compounds 1–3, coupled with comprehensive analyses of their X-ray diffraction data and variable-temperature ¹H NMR spectra collected in different solvents, allowed us to propose a general mechanism underlying the formation of inseparable C-24 epimers of hyperilongenol A (1), decipher the solvent effects on the enolizable β,β′-tricarbonyl enol protons, and explore the possibilities of keto–enol interconversions of compounds 1–3. Moreover, a reasonable proposal for the structural determination of PPAPs with enolizable β-dicarbonyl and β,β′-tricarbonyl systems was developed. In addition, an in vitro bioassay showed that 2 exhibited potent antibacterial activity against Staphylococcus aureus.

Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (±)-japonones A and B [(±)-1and (±)-2], were obtained fromHypericum japonicumThunb. The absolute configurations of (±)-1and (±)-2were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher’s methods and the assistance of quantum chemical predictions (QCP) of¹³C NMR chemical shifts. Among these metabolites, (+)-1exhibited some inhibitory activity on Kaposi’s sarcoma associated herpesvirus (KSHV). Virtual screening of (±)-1and (±)-2were conducted using the Surflex-Dock module in the Sybyl software and (+)-1exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99.