Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders.
Neurodegenerative diseases represent a challenge for biomedical research due to their high prevalence and lack of mechanism-based treatments. Because of the complex pathology of neurodegenerative disorders, multifunctional drugs have been increasingly recognized as potential treatments. We identified homobivalent γ-carbolinium salts as potent inihitors of both cholinesterases, N-methyl-D-aspartate receptors, and monoamine oxidases. Homobivalent γ-carbolines displayed similar structure-activity relationships on all tested targets and may present promising designed multiple ligands for the treatment of neurodegenerative disorders.
Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Jena , Philosophenweg 14, 07743 Jena, Germany.
Robert
R
Otto
Department of Pharmaceutical Biology, Institute of Pharmacy, University of Jena , Semmelweisstrasse 10, 07743 Jena, Germany.
Robert
R
Penzis
Department of Pharmaceutical Biology, Institute of Pharmacy, University of Jena , Semmelweisstrasse 10, 07743 Jena, Germany.
Friedemann
F
Gaube
Department of Anesthesiology, University Hospital of Ulm , Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Oliver
O
Adolph
Department of Anesthesiology, University Hospital of Ulm , Albert-Einstein-Allee 23, 89081 Ulm, Germany.
Karl J
KJ
Föhr
Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Jena , Philosophenweg 14, 07743 Jena, Germany.
Paul
P
Warncke
Institute of Pharmacy, Martin Luther University Halle-Wittenberg , Wolfgang-Langenbeck-Strasse 4, 06120 Halle/Saale, Germany.
Dina
D
Robaa
Institute of Pharmacology and Toxicology, University of Jena , Drackendorfer Strasse 1, 07747 Jena, Germany.
Dorothea
D
Appenroth
Institute of Pharmacology and Toxicology, University of Jena , Drackendorfer Strasse 1, 07747 Jena, Germany.
Christian
C
Fleck
Institute of Organic and Macromolecular Chemistry, Univerity of Jena , Humboldtstrasse 10, 07743 Jena, Germany.
Christoph
C
Enzensperger
Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy, University of Jena , Philosophenweg 14, 07743 Jena, Germany.
Jochen
J
Lehmann
Department of Pharmaceutical Biology, Institute of Pharmacy, University of Jena , Semmelweisstrasse 10, 07743 Jena, Germany.
Thomas
T
Winckler
D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis* / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019295:Computational Biology; D018691:Excitatory Amino Acid Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D002243:Carbolines; D002800:Cholinesterase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate