Structure-activity relationships of strychnine analogs at glycine receptors

Amal M Y Mohsen; Eberhard Heller; Ulrike Holzgrabe; Anders A Jensen; Darius P Zlotos

doi:10.1002/cbdv.201400110

Structure-activity relationships of strychnine analogs at glycine receptors

Chem Biodivers. 2014 Aug;11(8):1256-62. doi: 10.1002/cbdv.201400110.

Authors

Amal M Y Mohsen¹, Eberhard Heller, Ulrike Holzgrabe, Anders A Jensen, Darius P Zlotos

Affiliation

¹ 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.

PMID: 25146769
DOI: 10.1002/cbdv.201400110

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.

Keywords: Glycine receptors; Isostrychnine; Neostrychnine; Strychnidine; Strychnine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemistry Techniques, Synthetic
Humans
Inhibitory Concentration 50
Lactams / chemistry
Receptors, Glycine / antagonists & inhibitors*
Structure-Activity Relationship*
Strychnine / analogs & derivatives*

Substances

GLRB protein, human
Lactams
Receptors, Glycine
Strychnine