As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer’s disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC₅₀ values < 10 μM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.

Ferroptosis, an iron-dependent and lipid peroxidation-driven mode of regulated cell death, holds significant pathological significance. Its dysregulation manifests in dual facets: inhibition promotes tumorigenesis, whereas overactivation aggravates neurological disorders and organ injury. This paper systematically reviews the core molecular mechanisms of ferroptosis and provides a comprehensive summary of recent advances in its modulators: inducers classified by targets (GPX4 axis, iron metabolism, lipid metabolism, and GPX4-independent antioxidant pathways) and inhibitors classified by source (synthetic and natural). It places a particular focus on summarizing and analyzing the optimization strategies, mechanisms of action, existing limitations, and future directions for novel ferroptosis modulators, to offer valuable insights for future drug development targeting ferroptosis.

With the intensification of the population aging worldwide, neurological disorders (NDs) are seriously threatening human society. Mulberry, a traditional economic crop, is a significant medicinal plant. Increasing evidence suggests that phytochemicals from mulberry play critical roles in the prevention and treatment of NDs. This paper reviews the recently reported phytochemicals from mulberry with neuroprotective effects and systematically summarizes neuroprotective mechanisms and their classifications. Based on their origins from different parts of mulberry, the extracts with neuroprotective effects are classified into mulberry fruit extract and mulberry leaf extract. According to the compound structures, the compounds are divided into flavonoids, Diels–Alder-type adducts (DAAs), benzofurans, quinones, stilbenes, and alkaloids. This aims to provide a future reference for their pharmaceutical development and utilization.

Alzheimer disease (AD) is the most common form of dementia characterized by the loss of cognitive abilities through the death of central neuronal cells. In this study, structure-based virtual screens of 2 central nervous system-targeted libraries followed by molecular mechanics/generalized born surface area rescoring were performed to discover novel, selective butyrylcholinesterase (BChE) inhibitors, which are one of the most effective therapeutic strategies for the treatments in late-stage AD. Satisfyingly, compound 5 was identified as a highly selective low micromolar inhibitor of BChE (BChE IC₅₀ = 1.4 μM). The binding mode prediction and kinetic analysis were performed to obtain detailed information about compound 5. Besides, a preliminary structure–activity relationship investigation of compound 5 was carried out for further development of the series. The present results provided a valuable chemical template with a novel scaffold for the development of selective BChE inhibitors.