Rational approach to discover multipotent anti-Alzheimer drugs.
The coupling of two different pharmacophores, each endowed with different biological properties, afforded the hybrid compound lipocrine (7), whose biological profile was markedly improved relative to those of prototypes tacrine and lipoic acid. Lipocrine is the first compound that inhibits the catalytic activity of AChE and AChE-induced amyloid-beta aggregation and protects against reactive oxygen species. Thus, it emerged as a valuable pharmacological tool to investigate Alzheimer's disease and as a promising lead compound for new anti-Alzheimer drugs.
Rosini
Michela
M
Department of Pharmaceutical Sciences, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Andrisano
Vincenza
V
Bartolini
Manuela
M
Bolognesi
Maria L
ML
Hrelia
Patrizia
P
Minarini
Anna
A
Tarozzi
Andrea
A
Melchiorre
Carlo
C
D000110:Acetylcholinesterase / Q000737:chemistry; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002091:Butyrylcholinesterase / Q000737:chemistry; D002460:Cell Line; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D018697:Nootropic Agents; D017382:Reactive Oxygen Species; C540521:lipocrine; D013619:Tacrine; D008063:Thioctic Acid; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase