info@epichembio.eu + 34 986 812 316

Arndt Group. Organic synthesis.

ch.enzensperger@gmail.com
www.arndtgroup.uni-jena.de/Group+Members.html
Address
Humboldtstrasse 10, 07745 Jena
Germany
Keywords

Interaction between PARP and SIRT, NAD Metabolism, Epigenetic modulation. Neurodegenerative diseases; Dopamine and Serotonin Receptor ligands;

Models

Design and synthesis of new compound libraries

Techniques

Modern organic synthesis, Physicochemical characterization, LC/MS Identification of metabolites, Bio- and Chemoiformatics, Database mining, drug repositioning, SAR and cross-target SAR, Scaffold hopping, bioisosteric replacement, multi-target drugs

Collaborations outside COST

National Institute of Mental Health's Psychoactive Drug Screening Program (PDSP) The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI)

Short description of ongoing research projects

NAD Modulators as potential neuroprotectives and chemotherapeutics NAD acts as cofactor for redox systems, but is also an important regulator of sirtuins and poly-ADP-ribosylases (PARPs). Sirtuins regulate epigenetic factors, metabolism, genome stability and ageing, whereas PARPs are responsible for DNA repair, transcription regulation, mitosis and apoptotic processes. Since both classes of enzymes consume NAD, the modulation of the NAD anabolism and catabolism plays a crucial role in epigenetics and cellular signaling. In this project I synthesize focused libraries that address the NAD consumers PARP and SIRT. I also investigate the cross-target SARs among the NAD consuming targets and address both to gain cooperative biological effects. Azecines as potent dopamine- serotonin receptor ligands with D1/D5 selectivity Dopamine D1 and D5 receptor subtypes share a high overall, but seem to exhibit different physiological effects. The investigation of these different effects is difficult, because only a few slightly selective compounds are available. Several azecine derivatives are promising candidates for the development of either D1 or D5 selective compounds.

Publications
  1. Polanski W, Enzensperger C, Reichmann H, Gille G. The exceptional properties of 9-methyl-beta-carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti-inflammatory effects. J Neurochem. 2010, 113(6):1659-75
  2. Otto R, Penzis R, Gaube F, Adolph O, Föhr KJ, Warncke P, Robaa D, Appenroth D, Fleck C, Enzensperger C, Lehmann J, Winckler T. Evaluation of Homobivalent Carbolines as Designed Multiple Ligands for the Treatment of Neurodegenerative Disorders. J Med Chem. 2015; 58(16):6710-5
  3. Otto R, Gaube F, Penzis R, Appenroth D, Fleck C, Winckler T, Tränkle C, Lehmann J and Enzensperger C.* Beta and Gamma Carboline Derivatives as Potential Anti-Alzheimer Agents: A Comparison Eur J Med Chem. 2014, 87:63-70
  4. Gruss M, Appenroth D, Flubacher A, Enzensperger C, Bock J, Fleck C, Gille G, Braun K. 9-Methyl-ß-Carboline-Induced Cognitive Enhancement Is Associated With Elevated Hippocampal Dopamine Levels and Dendritic and Synaptic Proliferation. J Neurochem. 2012, 121(6):924-31
  5. Abdel-Fattah MA, Abadi AH, Lehmann J, Schweikert PM, Enzensperger C * D1-like receptors distinguishing thieno-azecine regioisomers Med Chem Commun. 2015, 6:1679-1686
Other activities of potential interest to others


Cost UE