Bernd Menzenbach
Schering AG
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Featured researches published by Bernd Menzenbach.
Steroids | 1997
Wolfgang Römer; Michael Oettel; Bernd Menzenbach; Peter Droescher; Sigfrid Schwarz
Abstract Antioxidant effects of N,N-dimethyl-p-toluidine, p-cresol, and p-(hydroxy)thioanisol 17α-substituted analogs of 17β-estradiol and their Δ9(11)-dehydro homologs were investigated using four different in vitro models: rat synaptosomal lipid peroxidation induced by Fentons reagent, Fe(II)-chelating activities, the formation of superoxide anion radicals, and total antioxidative activity. Whereas the classical estrogen 17β-estradiol as well as selected phenolic compounds was only moderately inhibiting iron-dependent lipid peroxidation and stimulating total antioxidative activity, besides Δ9(11)-dehydro-17β-estradiol (J 1213), novel estrogens such as C-17-oriented side chain analogs of 17β-estradiol (J 843, J 872, and J 897) and Δ9(11)-dehydro homologs (J 844, J 864, and J 898) directly altered the iron redox chemistry and diminished the formation of superoxide anion radicals generated by a xanthine/xanthine oxidase-dependent luminescence reaction to a great extent. These results suggest that definite modifications in the chemical structure of 17β-estradiol, e.g., the introduction of a Δ9(11)-double bond and/or p-cresol as well as p-(hydroxy)thioanisol C-17 substitution, may result in substantial changes in their antioxidant behavior. These compounds may be drug candidates for treating pathologies related to free radical formation.
Steroids | 2003
Alexander Hillisch; Johannes von Langen; Bernd Menzenbach; Peter Droescher; Günter Kaufmann; Birgitt Schneider; Walter Elger
Polar functional groups in the A- and D-ring (positions 3 and 17beta or 20) are common to all natural and synthetic steroid hormones. It was assumed that these pharmacophoric groups are involved in strong hydrogen bonding interactions with the respective steroid receptors. High resolution X-ray structures of the estrogen and androgen receptors have confirmed these assumptions. Also site-directed mutagenesis studies of the human progesterone receptor (hPR) suggest an important role for Cys891 in the recognition of the progesterone 20-carbonyl group. Surprisingly, the crystal structure of the hPR ligand binding domain (LBD) in complex with progesterone suggests that the carbonyl oxygen in position 20 (O20) is not involved in hydrogen bond contacts. To investigate these surprising and contradicting results further, we performed a molecular dynamics simulation of the hPR-progesterone complex in an aqueous environment. The simulation revealed hPR-Cys891 as the sole but weak hydrogen bonding partner of progesterone in the D-ring. In contrast to the site-directed mutagenesis data a major role of hPR-Cys891 in progesterone recognition could not be confirmed. Isolated hydrogen bond acceptors, such as the prosterone O20 group, in a relatively lipophilic environment of the receptor led to a decrease in affinity of the ligand. Based on this consideration and the structure of the PR, we designed compounds lacking such an acceptor function. If the X-ray structure and the calculations were right, these compounds should bind with comparable or higher affinity versus that of progesterone. E-17-Halomethylene steroids were synthesized and pharmacologically characterized in vitro and in vivo. Although the compounds are unable to form hydrogen bonds with the hPR in the D-ring region, they bind with superior affinity and exert stronger in vivo progestational effects than progesterone itself. Our investigations have confirmed the results of the X-ray structure and disproved the old pharmacophore model for progestogenic activity, comprising two essential polar functional groups on both ends of the steroid core. The 20-carbonyl group of progesterone is likely to play a role beyond PR-binding, e.g. in the context of other functions via the androgen and mineralocorticoid receptors and as a site of metabolic inactivation.
Archive | 1995
Helmut Dr Kasch; Gudrun Bertram; Kurt Ponsold; Gerd Schubert; Heidemarie Röhrig; Anatoli Kurischko; Bernd Menzenbach
Archive | 1998
Peter Droescher; Bernd Menzenbach; Wolfgang Roemer; Birgitt Schneider; Walter Elger; Guenter Kaufmann
Archive | 2004
Alexander Hillisch; Olaf Peters; Christian Gege; Gerhard Siemeister; Eberhard Unger; Bernd Menzenbach
Archive | 2006
Lars Wortmann; Arwed Cleve; Hans-Peter Muhn; Gernot Langer; Anna Schrey; Ronald Kühne; Bernd Menzenbach; Marcus Koppitz; Dirk Kosemund
Archive | 1994
Peter Droescher; Bernd Menzenbach; Kurt Ponsold; Bernd Undeutsch; Michael Oettel; Wolfgang Römer; Günter Kaufmann; Jens Schroder
Archive | 1994
Peter Droescher; Bernd Menzenbach; Kurt Ponsold; Bernd Undeutsch; Michael Oettel; Wolfgang Römer; Günter Kaufmann; Jens Schroder
Archive | 1994
Rolf-Dieter Hesch; Michael Oettel; Peter Droescher; Sigfrid Schwarz; Bernd Menzenbach; Wolfgang Römer; Günter Kaufmann; Jens Schroder
Archive | 1993
Helmut Kasch; Gudrun Bertram; Kurt Ponsold; Gerd Schubert; Heidemarie Röhrig; Anatoli Kurischko; Bernd Menzenbach