Phytochemistry2022，Vol.19413.DOI:10.1016/j.phytochem.2021.113017

Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): Identification of new structural scaffold for treatment of Alzheimer's disease

Vrabec, Rudolf Marikova, Jana Locarek, Miroslav Korabecny, Jan Hulcova, Daniela Hostalkova, Anna Kunes, Jiri Chlebek, Jakub Kucera, Tomas Hrabinova, Martina Jun, Daniel Soukup, Ondrej Andrisano, Vincenza Jenco, Jaroslav Safratova, Marcela Novakova, Lucie Opletal, Lubomir Cahlikova, Lucie
Phytochemistry2022，Vol.19413.DOI:10.1016/j.phytochem.2021.113017
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  • NSTL
  • Elsevier

Monoterpene indole alkaloids from Vinca minor L. (Apocynaceae): Identification of new structural scaffold for treatment of Alzheimer's disease

Vrabec, Rudolf 1Marikova, Jana 1Locarek, Miroslav 1Korabecny, Jan 2Hulcova, Daniela 1Hostalkova, Anna 1Kunes, Jiri 1Chlebek, Jakub 1Kucera, Tomas 2Hrabinova, Martina 2Jun, Daniel 2Soukup, Ondrej 2Andrisano, Vincenza 3Jenco, Jaroslav 1Safratova, Marcela 1Novakova, Lucie 1Opletal, Lubomir 1Cahlikova, Lucie1
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作者信息

  • 1. Charles Univ Prague
  • 2. Dept Toxicol & Mil Pharm
  • 3. Univ Bologna
  • 折叠

Abstract

One undescribed indole alkaloid together with twenty-two known compounds have been isolated from aerial parts of Vinca minor L. (Apocynaceae). The chemical structures of the isolated alkaloids were determined by a combination of MS, HRMS, 1D, and 2D NMR techniques, and by comparison with literature data. The NMR data of several alkaloids have been revised, corrected, and missing data have been supplemented. Alkaloids isolated in sufficient quantity were screened for their in vitro acetylcholinesterase (AChE; E.C. 3.1.1.7) and butyrylcholinesterase (BuChE; E.C. 3.1.1.8) inhibitory activity. Selected compounds were also evaluated for prolyl oligopeptidase (POP; E.C. 3.4.21.26), and glycogen synthase 3 beta-kinase (GSK-3 beta; E.C. 2.7.11.26) inhibition potential. Significant hBuChE inhibition activity has been shown by (- )-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1Hindole with an IC50 value of 0.65 +/- 0.16 mu M. This compound was further studied by enzyme kinetics, along with in silico techniques, to reveal the mode of inhibition. This compound is also predicted to cross the blood-brain barrier (BBB) through passive diffusion.

Key words

Vinca minor/Apocynaceae/Alzheimer's disease/Docking studies/Alkaloids/Butyrylcholinesterase/Vincaminorudeine/(-)-2-ethyl-3[2-(3-ethylpiperidinyl)-ethyl]-1H-indole/ENANTIOSELECTIVE TOTAL-SYNTHESIS/GLYCOGEN-SYNTHASE KINASE-3-BETA/PROLYL OLIGOPEPTIDASE/DIHYDROINDOLE ALKALOIDS/ABSOLUTE-CONFIGURATION/INHIBITORS/ACETYLCHOLINESTERASE/VINCADIFFORMINE/MINOVINE/CHOLINESTERASES

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出版年

2022
Phytochemistry

Phytochemistry

CCR
ISSN：0031-9422
被引量4
参考文献量98
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