Carolin Roegler

Friedrich Schiller University Jena, Jena, Thuringia, Germany

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Publications (9)20.76 Total impact

  • Carolin Roegler · Andreas König · Erika Glusa · Jochen Lehmann
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    ABSTRACT: Experimental studies on organic alkylnitrates have shown that both vasodilator potency and development of in vitro tolerance (tachyphylaxis) correlate with the number of nitrate groups in the molecule. However, introduction of an amino group to ethylnitrate yielded 2-nitrooxyethylammoniumnitrate (1), which is highly active but without inducing in vitro tolerance. Therefore, we prepared a series of aminoalkylnitrates and investigated vasorelaxation and tachyphylaxis on isolated prostaglandin F2alpha-precontracted porcine pulmonary arteries with intact endothelium. Tachyphylaxis was studied by incubating the arteries with EC100 of the respective aminoalkylnitrate and, after a 45-minute washout phase, measuring vasorelaxation again. All of the aminoalkylnitrates caused vasodilation, but the effect did not correlate with the number of nitrate moieties in the molecule. None of the substances was able to outperform compound 1, not even oligonitrates. Generally, structure–activity relationships found for alkylnitrates are obviously not valid for aminoalkylnitrates. Whereas the most potent aminomononitrate 1 evokes no in vitro tolerance, others exhibit tachyphylaxis independently of their vasodilator potency. We have shown that vasorelaxant activity and induction of tachyphylaxis are modulated significantly by introduction of an amino group to the alkylnitrate scaffold. Our results indicate that aminoalkylnitrates have to be considered as an individual class of nitrovasodilators with different structure–activity relationships and vasodilator properties.
    Journal of cardiovascular pharmacology 11/2010; 56(5):484-90. DOI:10.1097/FJC.0b013e3181f231da · 2.14 Impact Factor
  • Carolin Roegler · Jochen Lehmann
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    ABSTRACT: Sowohl organische Nitrate als auch Hemmstoffe der Phosphodiesterase 5 (PDE5) sind vasodilatatorische Substanzen. Whrend die zunchst als Sprengstoffe konzipierten organischen Nitrate als Antianginosa hauptschlich zur Behandlung der koronaren Herzkrankheit (KHK) genutzt werden, finden die ursprünglich zur Angina-pectoris-Therapie entwickelten PDE5-Hemmer Anwendung als Therapeutika der erektilen Dysfunktion sowie der pulmonalen Hypertonie.
    Pharmazie in unserer Zeit 09/2010; 39(5):351 - 358. DOI:10.1002/pauz.201000380
  • Christa E. Mueller · Carolin Roegler · Joerg Hockemeyer
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 10/2009; 40(40). DOI:10.1002/chin.200940155
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    Lei Fang · Carolin Roegler · Michael Decker · Yihua Zhang · Jochen Lehmann
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    ABSTRACT: This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at
    Bioorganic & medicinal chemistry letters 07/2009; DOI:10.1016/j.bmcl.2009.06.089 · 2.42 Impact Factor
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    ABSTRACT: The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012-dependent chemiluminescence and protein tyrosine nitration. Aminoethyl nitrate (AEN) showed an almost similar potency to glyceryl trinitrate (GTN), even though it is only a mononitrate. AEN-dependent vasodilatation was mediated by cGMP and nitric oxide. In contrast to triethanolamine trinitrate (TEAN) and GTN, AEN bioactivation did not depend on ALDH-2 and caused no in vitro tolerance. In vivo treatment with TEAN and GTN, but not with AEN, induced cross-tolerance to acetylcholine (ACh)-dependent and GTN-dependent relaxation. Although all nitrates tested induced tolerance to themselves, only TEAN and GTN significantly increased mitochondrial oxidative stress in vitro and in vivo. The present results demonstrate that not all high potency nitrates are bioactivated by ALDH-2 and that high potency of a given nitrate is not necessarily associated with induction of oxidative stress or nitrate tolerance. Obviously, there are distinct pathways for bioactivation of organic nitrates, which for AEN may involve xanthine oxidoreductase rather than P450 enzymes.
    British Journal of Pharmacology 07/2009; 158(2):510-20. DOI:10.1111/j.1476-5381.2009.00303.x · 4.84 Impact Factor
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    ABSTRACT: The vasodilators glyceryl trinitrate (GTN) and pentaerythrityl tetranitrate (PETN) are supposed to be degraded in vivo to the lower nitrates PETriN, PEDN, PEMN, 1,2-GDN, 1,3-GDN, 1-GMN, and 2-GMN. We synthesized these bioactive metabolites as reference compounds for pharmacokinetic studies. The use of HPLC-methods for monitoring the stepwise reduction of PETN to lower nitrates and the syntheses of the glyceryl dinitrates proved advantageous. Furthermore, we measured the vasorelaxant properties of all metabolites by performing organ bath experiments with porcine pulmonary arteries. In general, the vasodilator potency increases with the number of nitrate moieties in the compound.
    Bioorganic & medicinal chemistry letters 07/2009; 19(11):3141-4. DOI:10.1016/j.bmcl.2008.04.057 · 2.42 Impact Factor
  • Christa E. Müller · Carolin Roegler · Jörg Hockemeyer
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    ABSTRACT: A series of hydurilic acid derivatives (5,5′-bipyrimidinyl-2,4,6,2′,4′,6′-hexaones) including several new derivatives was synthesized from 5,6-diaminouracils. Mechanisms for their formation are proposed and discussed. Furthermore, a new method for the preparation of pyrimidine-2,4,5,6-tetraone-5-oxime derivatives (violuric acids) was found starting from 5-amino-6-nitrosouracils. © 2009 The Japan Institute of Heterocyclic Chemistry All rights reserved.
    Heterocycles 01/2009; 79(1). DOI:10.3987/COM-08-S(D)37 · 1.08 Impact Factor
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    ABSTRACT: In search of safer anti-Alzheimer drugs, 14 NO-donor-tacrine hybrids (1- 14) were synthesized and evaluated for their ability to inhibit cholinesterases and for vasorelaxation effects. Compounds 1- 13 showed good cholinesterases inhibitory activities in vitro, while 14, particularly, was highly selective, preferring butyrylcholinesterase rather than acetylcholinesterase. Four selected compounds (1, 9, 11, and 14) moderately relaxed the porcine pulmonary arteries in organ bath. In the hepatotoxicity study, significant hepatotoxicity was caused by tacrine but not by 9.
    Journal of Medicinal Chemistry 03/2008; 51(4):713-6. DOI:10.1021/jm701491k · 5.45 Impact Factor
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    ABSTRACT: The vasoactive properties of 14 organic mononitrates were investigated in vitro using PGF(2alpha)-precontracted porcine pulmonary arteries. A surprisingly wide range of vasorelaxant potencies was observed (pD(2): 3.36-7.50). Activities showed to be highly sensitive to the molecular structure and the substituents at the molecular carrier of the nitrate group. A correlation between lipophilicity and vasorelaxant potency could not be recognized. 2-Nitrooxyethylammoniumnitrate (1) was found to be slightly superior to the high potency trinitrate GTN.
    Bioorganic & Medicinal Chemistry Letters 12/2007; 17(21):5881-5. DOI:10.1016/j.bmcl.2007.08.046 · 2.42 Impact Factor