Development of Activity Rules and Chemical Fragment Design for In Silico Discovery of AChE and BACE1 Dual Inhibitors against Alzheimer's Disease.

Multi-target drug development has become an attractive strategy in the discovery of drugs to treat of Alzheimer's disease (AzD). In this study, for the first time, a rule-based machine learning (ML) approach with classification trees (CT) was applied for the rational design of novel dual-target acetylcholinesterase (AChE) and ß-site amyloid-protein precursor cleaving enzyme 1 (BACE1) inhibitors. Updated data from 3524 compounds with AChE and BACE1 measurements were curated from the ChEMBL database. The best global accuracies of training/external validation for AChE and BACE1 were 0.85/0.80 and 0.83/0.81, respectively. The rules were then applied to screen dual inhibitors from the original databases. Based on the best rules obtained from each classification tree, a set of potential AChE and BACE1 inhibitors were identified, and active fragments were extracted using Murcko-type decomposition analysis. More than 250 novel inhibitors were designed in silico based on active fragments and predicted AChE and BACE1 inhibitory activity using consensus QSAR models and docking validations. The rule-based and ML approach applied in this study may be useful for the in silico design and screening of new AChE and BACE1 dual inhibitors against AzD.

Comparison of the University Pharmacy Education Programs in Germany and Vietnam.

During the global COVID pandemic, the importance of professionals in the health care sector has been put in a new light, including pharmacists. In this context, the focus is also on how pharmacists are trained in different countries. Through an exchange of pharmacy teaching staff from a German to a Vietnamese university, the pharmacy education programs in both countries were compared. Aspects such as access to studies, structure of studies, and further training opportunities were considered. Differences and similarities emerged. In both countries, students first acquire basic knowledge and then delve deeper into pharmaceutical content in main studies. There is, expectedly, a great overlap in the content of the courses. Overall, the education at Vietnamese universities seems to be more practice-oriented due to a large number of placements. This also allows a specialization, which can be pursued in Germany with self-interest after graduation. There, the preparation for everyday work in the community pharmacy is separated from the university by a mandatory practical year. For the future, efforts are being made in both countries to strengthen the importance of clinical pharmacy in the curriculum. To this end, the Vietnamese are taking their inspiration from abroad in many cases, including Germany.