title: Structure-activity relationships of strychnine analogs at glycine receptors.
abstract: Nine strychnine derivatives including neostrychnine, strychnidine, isostrychnine, 21,22-dihydro-21-hydroxy-22-oxo-strychnine, and several hydrogenated analogs were synthesized, and their antagonistic activities at human α1 and α1β glycine receptors were evaluated. Isostrychnine has shown the best pharmacological profile exhibiting an IC50 value of 1.6 μM at α1 glycine receptors and 3.7-fold preference towards the α1 subtype. SAR Analysis indicates that the lactam moiety and the C(21) = C(22) bond in strychnine are essential structural features for its high antagonistic potency at glycine receptors.
authors.affiliation: The German University in Cairo, Department of Pharmaceutical Chemistry, New Cairo City, 11835 Cairo, Egypt (phone: +20 2 2758 1041; fax: +20 2 2758 1041). amal.yassin@guc.edu.eg.
authors.forename: Amal M Y
authors.initials: AM
authors.lastname: Mohsen
authors.forename: Eberhard
authors.initials: E
authors.lastname: Heller
authors.forename: Ulrike
authors.initials: U
authors.lastname: Holzgrabe
authors.forename: Anders A
authors.initials: AA
authors.lastname: Jensen
authors.forename: Darius P
authors.initials: DP
authors.lastname: Zlotos
mesh_terms: D060326:Chemistry Techniques, Synthetic; D006801:Humans; D020128:Inhibitory Concentration 50; D007769:Lactams / Q000737:chemistry; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013331:Strychnine / Q000031:analogs & derivatives*
chemical_list: C114561:GLRB protein, human; D007769:Lactams; D018009:Receptors, Glycine; D013331:Strychnine
keywords: Glycine receptors; Isostrychnine; Neostrychnine; Strychnidine; Strychnine