title: Synthesis and biochemical evaluation of highly enantiomerically pure (R,R)- and (S,S)-alexidine.
abstract: Alexidine is in everyday human use as oral disinfectant and contact lens disinfectant. It is used as a mixture of stereoisomers. Since all of alexidine's known biological targets are chiral, the biological activity of any of its chiral stereoisomers could be significantly higher than that of the mixture of stereoisomers. This makes a synthetic methodology for obtaining the individual enantiomers of the chiral diastereoisomer highly desirable. Here, we describe the first synthesis of both enantiomers of alexidine in high enantiomeric purity, and demonstrate their activity against the protein-protein interaction between the anti-apoptotic protein Bcl-xL and the pro-apoptotic protein Bak.
authors.affiliation: University of Leipzig, Institute of Organic Chemistry, Johannisallee 29, 04103 Leipzig, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Gröst
authors.forename: Martin
authors.initials: M
authors.lastname: Gräber
authors.forename: Michael
authors.initials: M
authors.lastname: Hell
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berg
mesh_terms: D001645:Biguanides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004202:Disinfectants / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D060066:Protein Interaction Maps / Q000187:drug effects*; D013237:Stereoisomerism; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001645:Biguanides; D004202:Disinfectants; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051020:bcl-X Protein; C001570:alexidine
keywords: Anti-apoptotic proteins; Chirality; Drug design; Inhibitors; Protein–protein interactions