Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids
A set of triterpenoids with different grades of oxidation in the lupane skeleton were prepared and evaluated as cholinesterase inhibitors. Allylic oxidation with selenium oxide and Jones's oxidation were employed to obtain mono-, di- and tri-oxolupanes, starting from calenduladiol (1) and lupeo...
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todo:paper_00452068_v79_n_p301_Castro2023-10-03T14:51:54Z Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids Castro, M.J. Richmond, V. Faraoni, M.B. Murray, A.P. Cholinesterase inhibitors Lupane derivatives Molecular modeling Triterpenoids 16beta hydroxy 3 oxo lup 1,20(29) dien 30 al 16beta hydroxy 3 oxo lup 20(29) en 30 al 16beta hydroxy lup 20(29) en 3 one 3 oxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) ene 3beta hydroxy 16 oxo lup 20(29) en 30 al 3beta hydroxy lup 20(29) en 16 one 3beta hydroxy lup 20(29) en 30 al 3beta,16beta dihydroxy lup 20(29) en 30 al calenduladiol cholinesterase inhibitor lup 20(29) en 3 one lupeol natural product selenium oxide triterpene unclassified drug acetylcholinesterase cholinesterase cholinesterase inhibitor lupane triterpene Acacia Acacia cedilloi Article carbon nuclear magnetic resonance cholinesterase inhibition column chromatography competitive inhibition drug synthesis enzyme activity enzyme inhibitor complex hydrogen bond IC50 mass spectrometry molecular docking molecular dynamics molecular model nonhuman oxidation priority journal proton nuclear magnetic resonance animal chemical structure chemistry dose response human metabolism oxidation reduction reaction structure activity relation synthesis Torpedo Acetylcholinesterase Animals Butyrylcholinesterase Cholinesterase Inhibitors Dose-Response Relationship, Drug Humans Molecular Docking Simulation Molecular Structure Oxidation-Reduction Structure-Activity Relationship Torpedo Triterpenes A set of triterpenoids with different grades of oxidation in the lupane skeleton were prepared and evaluated as cholinesterase inhibitors. Allylic oxidation with selenium oxide and Jones's oxidation were employed to obtain mono-, di- and tri-oxolupanes, starting from calenduladiol (1) and lupeol (3). All the derivatives showed a selective inhibition of butyrylcholinesterase over acetylcholinesterase (BChE vs. AChE). A kinetic study proved that compounds 2 and 9, the more potent inhibitors of the series, act as competitive inhibitors. Molecular modeling was used to understand their interaction with BChE, the role of carbonyl at C-16 and the selectivity towards this enzyme over AChE. These results indicate that oxidation at C-16 of the lupane skeleton is a key transformation in order to improve the cholinesterase inhibition of these compounds. © 2018 Elsevier Inc. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00452068_v79_n_p301_Castro |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cholinesterase inhibitors Lupane derivatives Molecular modeling Triterpenoids 16beta hydroxy 3 oxo lup 1,20(29) dien 30 al 16beta hydroxy 3 oxo lup 20(29) en 30 al 16beta hydroxy lup 20(29) en 3 one 3 oxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) ene 3beta hydroxy 16 oxo lup 20(29) en 30 al 3beta hydroxy lup 20(29) en 16 one 3beta hydroxy lup 20(29) en 30 al 3beta,16beta dihydroxy lup 20(29) en 30 al calenduladiol cholinesterase inhibitor lup 20(29) en 3 one lupeol natural product selenium oxide triterpene unclassified drug acetylcholinesterase cholinesterase cholinesterase inhibitor lupane triterpene Acacia Acacia cedilloi Article carbon nuclear magnetic resonance cholinesterase inhibition column chromatography competitive inhibition drug synthesis enzyme activity enzyme inhibitor complex hydrogen bond IC50 mass spectrometry molecular docking molecular dynamics molecular model nonhuman oxidation priority journal proton nuclear magnetic resonance animal chemical structure chemistry dose response human metabolism oxidation reduction reaction structure activity relation synthesis Torpedo Acetylcholinesterase Animals Butyrylcholinesterase Cholinesterase Inhibitors Dose-Response Relationship, Drug Humans Molecular Docking Simulation Molecular Structure Oxidation-Reduction Structure-Activity Relationship Torpedo Triterpenes |
| spellingShingle |
Cholinesterase inhibitors Lupane derivatives Molecular modeling Triterpenoids 16beta hydroxy 3 oxo lup 1,20(29) dien 30 al 16beta hydroxy 3 oxo lup 20(29) en 30 al 16beta hydroxy lup 20(29) en 3 one 3 oxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) ene 3beta hydroxy 16 oxo lup 20(29) en 30 al 3beta hydroxy lup 20(29) en 16 one 3beta hydroxy lup 20(29) en 30 al 3beta,16beta dihydroxy lup 20(29) en 30 al calenduladiol cholinesterase inhibitor lup 20(29) en 3 one lupeol natural product selenium oxide triterpene unclassified drug acetylcholinesterase cholinesterase cholinesterase inhibitor lupane triterpene Acacia Acacia cedilloi Article carbon nuclear magnetic resonance cholinesterase inhibition column chromatography competitive inhibition drug synthesis enzyme activity enzyme inhibitor complex hydrogen bond IC50 mass spectrometry molecular docking molecular dynamics molecular model nonhuman oxidation priority journal proton nuclear magnetic resonance animal chemical structure chemistry dose response human metabolism oxidation reduction reaction structure activity relation synthesis Torpedo Acetylcholinesterase Animals Butyrylcholinesterase Cholinesterase Inhibitors Dose-Response Relationship, Drug Humans Molecular Docking Simulation Molecular Structure Oxidation-Reduction Structure-Activity Relationship Torpedo Triterpenes Castro, M.J. Richmond, V. Faraoni, M.B. Murray, A.P. Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| topic_facet |
Cholinesterase inhibitors Lupane derivatives Molecular modeling Triterpenoids 16beta hydroxy 3 oxo lup 1,20(29) dien 30 al 16beta hydroxy 3 oxo lup 20(29) en 30 al 16beta hydroxy lup 20(29) en 3 one 3 oxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) en 30 al 3,16 dioxo lup 20(29) ene 3beta hydroxy 16 oxo lup 20(29) en 30 al 3beta hydroxy lup 20(29) en 16 one 3beta hydroxy lup 20(29) en 30 al 3beta,16beta dihydroxy lup 20(29) en 30 al calenduladiol cholinesterase inhibitor lup 20(29) en 3 one lupeol natural product selenium oxide triterpene unclassified drug acetylcholinesterase cholinesterase cholinesterase inhibitor lupane triterpene Acacia Acacia cedilloi Article carbon nuclear magnetic resonance cholinesterase inhibition column chromatography competitive inhibition drug synthesis enzyme activity enzyme inhibitor complex hydrogen bond IC50 mass spectrometry molecular docking molecular dynamics molecular model nonhuman oxidation priority journal proton nuclear magnetic resonance animal chemical structure chemistry dose response human metabolism oxidation reduction reaction structure activity relation synthesis Torpedo Acetylcholinesterase Animals Butyrylcholinesterase Cholinesterase Inhibitors Dose-Response Relationship, Drug Humans Molecular Docking Simulation Molecular Structure Oxidation-Reduction Structure-Activity Relationship Torpedo Triterpenes |
| description |
A set of triterpenoids with different grades of oxidation in the lupane skeleton were prepared and evaluated as cholinesterase inhibitors. Allylic oxidation with selenium oxide and Jones's oxidation were employed to obtain mono-, di- and tri-oxolupanes, starting from calenduladiol (1) and lupeol (3). All the derivatives showed a selective inhibition of butyrylcholinesterase over acetylcholinesterase (BChE vs. AChE). A kinetic study proved that compounds 2 and 9, the more potent inhibitors of the series, act as competitive inhibitors. Molecular modeling was used to understand their interaction with BChE, the role of carbonyl at C-16 and the selectivity towards this enzyme over AChE. These results indicate that oxidation at C-16 of the lupane skeleton is a key transformation in order to improve the cholinesterase inhibition of these compounds. © 2018 Elsevier Inc. |
| format |
JOUR |
| author |
Castro, M.J. Richmond, V. Faraoni, M.B. Murray, A.P. |
| author_facet |
Castro, M.J. Richmond, V. Faraoni, M.B. Murray, A.P. |
| author_sort |
Castro, M.J. |
| title |
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| title_short |
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| title_full |
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| title_fullStr |
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| title_full_unstemmed |
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| title_sort |
oxidation at c-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids |
| url |
http://hdl.handle.net/20.500.12110/paper_00452068_v79_n_p301_Castro |
| work_keys_str_mv |
AT castromj oxidationatc16enhancesbutyrylcholinesteraseinhibitioninlupanetriterpenoids AT richmondv oxidationatc16enhancesbutyrylcholinesteraseinhibitioninlupanetriterpenoids AT faraonimb oxidationatc16enhancesbutyrylcholinesteraseinhibitioninlupanetriterpenoids AT murrayap oxidationatc16enhancesbutyrylcholinesteraseinhibitioninlupanetriterpenoids |
| _version_ |
1807318179110715392 |