biostudies-literatureSchino IFundação para a Ciencia e a Tecnologia54https://www.ebi.ac.uk/biostudies/studies/S-EPMC9864808biostudies-literatureUnknown16(1)Alzheimer's Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N⁷/N⁹ linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N⁹-linked 6-deoxy-αPharmaceuticals (Basel, Switzerland)Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer's Disease.PMC9864808UIDB/00100/2020, LA/P/0056/2020, PTDC/QUI-QFI/29527/2017Altomare CDBarros JMaria CSchino ICantore MColabufo NAShimizu KLopes JNCCalado Pde Candia MRauter APOliveira MCCachatra VFreitas AAFerreira MJfalseExploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer's Disease.Alzheimer's Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N⁷/N⁹ linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N⁹-linked 6-deoxy-α2022-01-01T00:00:00Z2022 Dec2025-05-31T23:49:41.766Z2025-05-31T23:49:41.766ZS-EPMC98648083667855210.3390/ph16010054