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Synthesis, biochemi...
Synthesis, biochemical, pharmacological characterization and in silico profile modelling of highly potent opioid orvinol and thevinol derivatives
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- Szucs, Edina (författare)
- Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary.;Univ Szeged, Fac Med, Doctoral Sch Theoret Med, Dom Ter 10, H-6720 Szeged, Hungary.
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- Marton, Janos (författare)
- Biomed Forschungsreagenzien GmbH, ABX Adv Biochem Cpds, Heinrich Glaeser Str 10-14, D-01454 Radeberg, Germany.
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- Szabo, Zoltan (författare)
- KTH,Organisk kemi
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visa fler...
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- Hosztafi, Sandor (författare)
- Semmelweis Univ, Inst Pharmaceut Chem, Hogyes Endre Utca 9, H-1092 Budapest, Hungary.
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- Kekesi, Gabriella (författare)
- Univ Szeged, Fac Med, Dept Physiol, Dom Ter 10, H-6720 Szeged, Hungary.
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- Tuboly, Gabor (författare)
- Univ Szeged, Fac Med, Dept Neurol, Semmelweis U 6, H-6725 Szeged, Hungary.
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- Banki, Laszlo (författare)
- Univ Szeged, Fac Med, Dept Traumatol, Semmelweis U 6, H-6725 Szeged, Hungary.
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- Horvath, Gyongyi (författare)
- Univ Szeged, Fac Med, Dept Physiol, Dom Ter 10, H-6720 Szeged, Hungary.
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- Szabo, Pal T. (författare)
- Res Ctr Nat Sci, MS Metabol Res Lab, Magyar Tudosok Krt 2, H-1117 Budapest, Hungary.
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- Tomboly, Csaba (författare)
- Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary.
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- Varga, Zsuzsanna Katalin (författare)
- Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary.;Univ Szeged, Fac Med, Doctoral Sch Theoret Med, Dom Ter 10, H-6720 Szeged, Hungary.
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- Benyhe, Sandor (författare)
- Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary.
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- Otvos, Ferenc (författare)
- Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary.
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Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary;Univ Szeged, Fac Med, Doctoral Sch Theoret Med, Dom Ter 10, H-6720 Szeged, Hungary. Biomed Forschungsreagenzien GmbH, ABX Adv Biochem Cpds, Heinrich Glaeser Str 10-14, D-01454 Radeberg, Germany. (creator_code:org_t)
- ELSEVIER, 2020
- 2020
- Engelska.
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Ingår i: European Journal of Medicinal Chemistry. - : ELSEVIER. - 0223-5234 .- 1768-3254. ; 191
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Morphine and its derivatives play inevitably important role in the m-opioid receptor (MOR) targeted antinociception. A structure-activity relationship study is presented for novel and known orvinol and thevinol derivatives with varying 3-O, 6-O, 17-N and 20-alkyl substitutions starting from agonists, antagonists and partial agonists. In vitro competition binding experiments with [H-3]DAMGO showed low subnanomolar affinity to MOR. Generally, 6-O-demethylation increased the affinity toward MOR and decreased the efficacy changing the pharmacological profile in some cases. In vivo tests in osteoarthritis inflammation model showed significant antiallodynic effects of thevinol derivatives while orvinol derivatives did not. The pharmacological character was modelled by computational docking to both active and inactive state models of MOR. Docking energy difference for the two states separates agonists and antagonists well while partial agonists overlapped with them. An interaction pattern of the ligands, involving the interacting receptor atoms, showed more efficient separation of the pharmacological profiles. In rats, thevinol derivatives showed antiallodynic effect in vivo. The orvinol derivatives, except for 6-O-desmethyl-dihydroetorfin (2c), did not show antiallodynic effect.
Ämnesord
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- G-protein
- Efficacy
- Binding
- Mu-opioid
- Osteoarthritis inflammation model
- Interaction fingerprint
- 6
- 14-Ethenomorphinan derivatives
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- ref (ämneskategori)
- art (ämneskategori)
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Szucs, Edina
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Marton, Janos
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Szabo, Zoltan
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Hosztafi, Sandor
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Kekesi, Gabriell ...
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Tuboly, Gabor
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visa fler...
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Banki, Laszlo
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Horvath, Gyongyi
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Szabo, Pal T.
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Tomboly, Csaba
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Varga, Zsuzsanna ...
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Benyhe, Sandor
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Otvos, Ferenc
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visa färre...
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