11-Aminostrychnine and N-(Strychnine-11-yl)propionamide: Synthesis, Configuration, and Pharmacological Evaluation at Glycine Receptors
- Resource Type
- Article
- Authors
- Zlotos, Darius P.; Mohsen, Amal M. Y.; Mandour, Yasmine M.; Marzouk, Mohamed A.; Breitinger, Ulrike; Villmann, Carmen; Breitinger, Hans-Georg; Sotriffer, Christoph; Jensen, Anders A.; Holzgrabe, Ulrike
- Source
- Journal of Natural Products; August 2019, Vol. 82 Issue: 8 p2332-2336, 5p
- Subject
- Language
- ISSN
- 01633864; 15206025
(11S)-11-Aminostrychnine (1) and N-[(11S)-strychnine-11-yl]propionamide (2) were synthesized and characterized as antagonists of homomeric α1 and heteromeric α1β glycine receptors in a functional fluorescence-based assay and a patch-clamp assay and in radioligand binding studies. The absolute configuration at C-11 of 1was determined based on vicinal coupling constants and NOESY data. Docking experiments to the orthosteric binding site of the α3 glycine receptor showed a binding mode of compound 2analogous to that of strychnine, explaining its high antagonistic potency. The findings identify the C-11 amide function of strychnine as a suitable linker group for the future development of dimeric strychnine analogues targeting glycine receptors. The findings extend the SAR of strychnine at glycine receptors.