title: Design and synthesis of novel 1,4-benzodiazepine derivatives and their biological evaluation as cholinesterase inhibitors.
abstract: A new series of 1,4-benzodiazepine-2,5-dione structurally related to cyclopenin has been synthesized. The new compounds were assayed in vivo and in vitro for their ability to inhibit acetylcholinesterase enzyme and were found to have potent reversible anticholinesterase activity when tested in vitro for isolated frog rectus abdominis and guinea pig ileum in addition to increasing brain cholinesterase level in rats when percentage inhibition were tested in vivo, moreover compounds 5a, 5b, 5c and 5g were the most active. LD(50) was performed for these derivatives and they displayed high safety margin.
authors.affiliation: Department of Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. lamiawagdy@hotmail.com
authors.forename: Lamia Wagdy
authors.initials: LW
authors.lastname: Mohamed
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: El-Yamany
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001001:Anura; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D001569:Benzodiazepines; D000110:Acetylcholinesterase