title: Synthesis and biological evaluation of NO-donor-tacrine hybrids as hepatoprotective anti-Alzheimer drug candidates.
abstract: In search of safer anti-Alzheimer drugs, 14 NO-donor-tacrine hybrids (1- 14) were synthesized and evaluated for their ability to inhibit cholinesterases and for vasorelaxation effects. Compounds 1- 13 showed good cholinesterases inhibitory activities in vitro, while 14, particularly, was highly selective, preferring butyrylcholinesterase rather than acetylcholinesterase. Four selected compounds (1, 9, 11, and 14) moderately relaxed the porcine pulmonary arteries in organ bath. In the hepatotoxicity study, significant hepatotoxicity was caused by tacrine but not by 9.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.forename: Dorothea
authors.initials: D
authors.lastname: Appenroth
authors.forename: Michael
authors.initials: M
authors.lastname: Decker
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
authors.forename: Carolin
authors.initials: C
authors.lastname: Roegler
authors.forename: Thomas
authors.initials: T
authors.lastname: Deufel
authors.forename: Christian
authors.initials: C
authors.lastname: Fleck
authors.forename: Sixun
authors.initials: S
authors.lastname: Peng
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jochen
authors.initials: J
authors.lastname: Lehmann
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009126:Muscle Relaxation; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D013552:Swine; D013619:Tacrine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D002800:Cholinesterase Inhibitors; D020030:Nitric Oxide Donors; D013619:Tacrine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase