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Vorträge und Posterpräsentationen (ohne Tagungsband-Eintrag):

G. Pototschnig, M. Haider, S. Khom, S. Hering, M.D. Mihovilovic:
"Valerenic Acid as lead compound for the development of novel GABAA receptor ligands";
Poster: Gordon Research Conference on Natural Products, Andover, NH, United States; 26.07.2015 - 31.07.2015.



Kurzfassung englisch:
Anxiety and panic disorders are amongst the most common mental diseases worldwide.
Most effectively, these diseases are treated with benzodiazepines. However, these compounds are known to cause severe side effects like confusion, fatigue and drug addiction.

Valerenic acid, a sesquiterpenoidal compound isolated from roots of Valeriana officinalis, acts as subtype selective allosteric ligand on the GABAA receptor.1 The highly pronounced selectivity for β2/3 over β1 subunits allows for addressing anxiety rather than sedation in animal models.2 Therefore, Valerenic acid could serve as alternative for benzodiazepines for the treatment of anxiety.

To gain insight into the so far unknown binding mode and mode of action of Valerenic acid derived GABAA receptor ligands different regions of the complex original structure were modified (Figure 1).











Fig. 1: Modifications of the original Valerenic acid structure.

Based on the total synthesis of Valerenic acid3, a set of compounds was synthesized and biologically evaluated via electrophysiology.
Results from the above mentioned structural alterations, in regions and functionalities, could give insight in the ligand - receptor interaction and elucidate structural motifs necessary for binding.
We plan to further optimize the structure in terms of synthetic feasibility and biological activity.


REFERENCES

1. Khom, S.; Baburin, I.; Timin, E.; Hohaus, A.; Trauner. G.; Kopp, B.; Hering, S. Neuropharmacology, 2007, 53, 178-187.
2. Khom, S.; Strommer, B.; Ramharter, J.; Schwarz, T.; Schwarzer, C.; Erker, T.; Ecker, G. F.; Mulzer, J.; Hering, S., Br J Pharmacol 2010, 161, 65-78.
3. Ramharter, J.; Mulzer, J. Organic Letters, 2009, 11, 1151-1153.

Erstellt aus der Publikationsdatenbank der Technischen Universität Wien.