Natural product-derived ferroptosis mediators.

It has been 11 years since ferroptosis, a new mode of programmed cell death, was first proposed. Natural products are an important source of drug discovery. In the past five years, natural product-derived ferroptosis regulators have been discovered in an endless stream. Herein, 178 natural products discovered so far to trigger or resist ferroptosis are classified into 6 structural classes based on skeleton type, and the mechanisms of action that have been reported are elaborated upon. If pharmacodynamic data are sufficient, the structure and bioactivity relationship is also presented. This review will provide medicinal chemists with some effective ferroptosis regulators, which will promote the research of natural product-based treatment of ferroptosis-related diseases in the future.

Rare 7,9'-dinorlignans with neuroprotective activity from the roots of Lindera aggregata (Sims) Kosterm.

Linderagatins C-F (1-4), the first examples of naturally occurring diaryltetrahydrofuran-type 7,9'-dinorlignans, were characterized from the roots of Lindera aggregata (Sims) Kosterm. The structures of these dinorlignans were elucidated by extensive spectroscopic analysis. The absolute configurations were determined based on calculated and experimental ECD data. A biosynthetic pathway for these dinorlignans was hypothetically proposed. Compounds 2 and 3 showed significant neuroprotective effects on erastin-induced ferroptosis in HT-22 cells with EC50 values of 23.4 and 21.8 µM, respectively.

Discovery of phenylcarbamoyl xanthone derivatives as potent neuroprotective agents for treating ischemic stroke.

Compounds of natural sources are widespread discovered in the treatment of ischemic stroke. Alpha-mangostin, a natural prenylated xanthone, has been found to display a therapeutic potential to treat ischemic stroke. However, the direct application of α-mangostin is limited due to its cytotoxicity and relatively low efficacy. Herein, structural modification of α-mangostin was necessary to improve its drug-ability. Currently, 34 α-mangostin phenylcarbamoyl derivatives were synthesized and evaluated for their neuroprotective activities by glutamate-induced excitotoxicity and H2O2-induced oxidative damage models in vitro. The results showed that compound 2 had the most therapeutic potential in both models. Whereafter, 2 has been proved to have powerful therapeutic effects by the MCAO ischemic stroke model in rats, which might be due to inhibition of inflammatory reaction and free radical accumulation. Besides, acute toxicity assay in rats showed that compound 2 had excellent safety. Overall, 2 could be a promising neuroprotective agent for the treatment of ischemic stroke deserving further investigations.