Lachhab_2026_Mol.Divers__

Recent studies suggest that Alzheimer's disease may be influenced by microbial infections and may involve multiple microbial pathogens contributing to its development and progression. Based on this hypothesis, dual antimicrobial and anti-Alzheimer's agents may provide advantages such as improved therapeutic effectiveness, treatment of infection-related Alzheimer disease, and reduced toxicity compared with single-target drugs. To discover novel therapeutic agents, a series of terpene-substituted pyrimidine derivatives were synthesized and evaluated for their antiviral, antibacterial, antifungal and anti-Alzheimer's activities. All compounds were characterized by spectroscopic methods to support their structures. Among all compounds screened for their biological activity, compounds 11 and 32 displayed excellent IC50 values of 10.1 and 9.9 microM, respectively, against eqBChE in comparison with Food and Drug Administration (FDA)-approved drugs galantamine (IC(50) = 20.6 microM) and donepezil (IC(50) = 4.1 microM) for the treatment of Alzheimer's disease (AD). Additionally, compound 32 exhibited promising antifungal activity against C. tropicalis (MIC = 0.83 micromol/ml and MFC = 1.69 micromol/ml), showing two-fold greater potency than fluconazole and three-fold greater potency than 5-fluorocytosine. Moreover, terpene derivative 32 showed moderate antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis, with MIC and MBC values ranging from 3.35 to 6.71 micromol/ml. The docking studies of 32 with eqBChE supported the observed in vitro results. This study provides a promising lead compound with dual antimicrobial and anti-Alzheimer activity that may be further developed as a potential therapeutic agent for the treatment of Alzheimer's disease.