biostudies-literatureUnknown15(9)Hung NVAlzheimer's disease (AD) is associated with AChE and BACE1 enzymes. Designing inhibitors for preventing these enzymes can be benefit for AD treatment. In this context, theophylline derivatives were generated to prevent the biological activity of AChE and BACE1. In particular, the potential inhibitory of these compounds was rapidly and accurately estimated <i>via</i> knowledge-methods. The <i>in vitro</i> tests were then performed to validate the artificial intelligent approach. Among these, compound 12 exhibited the most potent AChE inhibition with an IC₅₀ of 15.68 μM, while showing limited activity against BACE1. In addition, six compounds were indicated that are able to inhibit AChE, however, the theophylline derivatives play poor performance over the BACE1 target. Atomistic sRSC advances6994-7003https://www.ebi.ac.uk/biostudies/studies/S-EPMC11877286biostudies-literatureDiscovery of novel theophylline derivatives bearing tetrazole scaffold for the treatment of Alzheimer's disease.PMC11877286Hien TTTTran PTNguyen THHung NVThai QMHai Linh VNQuoc Tien LNgo STHoang VHNguyen TXTran HNguyen TKPham DVfalseDiscovery of novel theophylline derivatives bearing tetrazole scaffold for the treatment of Alzheimer's disease.Alzheimer's disease (AD) is associated with AChE and BACE1 enzymes. Designing inhibitors for preventing these enzymes can be benefit for AD treatment. In this context, theophylline derivatives were generated to prevent the biological activity of AChE and BACE1. In particular, the potential inhibitory of these compounds was rapidly and accurately estimated <i>via</i> knowledge-methods. The <i>in vitro</i> tests were then performed to validate the artificial intelligent approach. Among these, compound 12 exhibited the most potent AChE inhibition with an IC₅₀ of 15.68 μM, while showing limited activity against BACE1. In addition, six compounds were indicated that are able to inhibit AChE, however, the theophylline derivatives play poor performance over the BACE1 target. Atomistic s2025-01-01T00:00:00Z2025 Feb2026-06-02T00:00:42.882Z2025-04-04T20:25:02.727ZS-EPMC118772864004137710.1039/d5ra00488h