Naphtho-γ-pyrone Dimers from an Endozoic Aspergillus niger and the Effects of Coisolated Monomers in Combination with Cisplatin on a Cisplatin-Resistant A549 Cell Line

Abstract

Chemotherapy resistance is one of the main causes of lung cancer treatment failure, and a combination regimen may be an effective way to overcome this. Here we report 5 new (1–3, 7, and 9) and 15 known polyketides, isolated from an endozoic Aspergillus niger. The structures of the new compounds were determined by the interpretation of IR, HRESIMS, NMR, and ECD spectra. The ESI-MS/MS fragmentation of the isolated naphtho-γ-pyrone isomers in positive mode is discussed. The effects of isolated compounds in combination with cisplatin (DDP) on a DDP-resistant A549 cell line (A459/DDP) are investigated. The most active compound, 12, could reduce the ratio of GSH/GSSG, promote the generation of intracellular ROS, and cooperate with DDP to down-regulated levels of Nrf2, Akt, HO-1, and NQO1, suggesting that inhibition of Nrf2 and Akt pathways might be involved in the combined effect of 12 and DDP in A549/DDP cells.

Undescribed Meroterpenoids from Hypericum japonicum with Neuroprotective Effects on H2O2 Insult SH‐SY5Y Cells Targeting Keap1‐Nrf2

“…All metabolites possessed the phloroglucinol and Michael acceptors molecule traits, which generally featured as lead compounds via activating the signaling pathway of Keap1‐Nrf2‐ARE, [ 34 ] and Nrf2 regulates intracellular levels of ROS and glutathione (GSH). [ 35 ] ROS plays a key role during neurodegenerative maladies, generally breaches the intracellular redox homeostasis, and induces neuronal cells apoptosis. [ 3,36 ] Glutathione (GSH) reduces intracellular harmful chemicals such as peroxides, epoxides, and free radicals to protect cells from oxidative damage.…”