Martin Luther University Halle-Wittenberg

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Protoberberine alkaloids

Mainly occurring in plants of the Papaveraceae family, this class of alkaloids is characterised by a tetracyclic ring system which 'hides' a substituted phenethylamine or vanillylamine, depending on viewing 'angle'. The protoberberine alkaloids have (too) many effects, none of them so pronounced that it would be of considerable therapeutic benefit. So far, only a few protoberberines and plant extracts containing them were used medicinally, namely as psychoactive drugs or sedatives. We try to 'extract' and increase effects they have by chemical synthesis of new derivatives and by isolation from plants. In doing this, we thoroughly examined each step required to construct the tetracyclic system, to improve yields, and to explore to the limits and possibilities of ring closures with various substituents. Our protoberberines proved to be very useful in detailed studies of the substrate requirements of CYP isoenzymes, studies undertaken in context of a cooperation with a research group in Finland. CYP are among the most important metabolic enzymes in humans.

Cooperations:

Prof. Dr. Franz Bracher, Department Pharmazie, Zentrum für Pharmaforschung, Ludwig-Maximilians-Universität, München

Prof. Dr. Hannu Raunio, Department of Pharmacology and Toxicology, University of Eastern Finland, Kuopio, Finland

PhD and Diploma Theses:

A. Meyer, PhD Thesis Halle 2008

A. Horling, PhD Thesis, in preparation.

Publications:

A. Meyer, P. Imming, R (-)-Canadaline as first alkaloid from Corydalis cava secoberbine. Phytochemistry Lett. 2008, 1, 168-170. doi:10.1016/j.phytol.2008.07.006   

K. A. Salminen, A. Meyer, L. Jerabkova, L. E. Korhonen, M. Rahnasto, R. O. Juvonen, P. Imming, H. Raunio, Inhibition of human drug metabolizing cytochrome P450 enzymes by isoquinoline alkaloids plans. Phytomedicine 2011, 18, 533-538. doi:10.1016/j.phymed.2010.08.012   

K. A. Salminen, A. Meyer, P. Imming, H. Raunio, CYP2C19 progress curve analysis and mechanism-based inactivation by three methylenedioxyphenyl compounds. Drug Metabolism and Disposition 2011, 39, 2283-2289. doi:10.1124/dmd.111.041319   

A. Meyer, P. Imming, Benzylisoquinoline alkaloids from the Papaveraceae: The Heritage of Johannes Gadamer (1867-1928). J. Nat. Prod 2011, 74, 2482-2487. doi:10.1021/np2005049   

A. Horling, C. Müller, R. Barthel, F. Bracher, P. Imming, A New Class of Selective and Potent 7 Dehydrocholesterol Reductase Inhibitors. J. Med. Chem. 2012, 55, 7614–7622. doi:10.1021/jm3006096   

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