Interaction between PARP and SIRT, NAD Metabolism, Epigenetic modulation. Neurodegenerative diseases; Dopamine and Serotonin Receptor ligands;
Design and synthesis of new compound libraries
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
National Institute of Mental Health's Psychoactive Drug Screening Program (PDSP) The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI)
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.