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Effect of chiral polyhydrochromenes on cannabinoid system

  • Nikolai S. Li-Zhulanov
  • Irina V. Il’ina
  • Andrea Chicca
  • Patricia Schenker
  • Oksana S. Patrusheva
  • Ekaterina V. Nazimova
  • Dina V. Korchagina
  • Mikhail Krasavin
  • Konstantin P. VolchoEmail author
  • Nariman F. Salakhutdinov
Original Research
  • 59 Downloads

Abstract

A set of chiral polyhydrochromenes was synthesized by clay-catalyzed reactions of monoterpenoids (−)-isopulegol, (+)-neoisopulegol and (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 5 with aromatic and heteroaromatic aldehydes. These compounds resemble in structure phytocannabinoids, some of them demonstrated analgesic activity in vivo. Polyhydrochromenes containing amino groups were obtained through the interaction of (−)-isopulegol with 5-hydroxymethylfurfural, followed by substitution of hydroxy-group with bromine and further reaction with amines. The ability of all synthesized compounds to influence the endocannabinoid system was studied for the first time. Although the polyhydrochromenes did not significantly bind to CB1 and CB2 cannabinoid receptors and did not inhibit MAGL activity at the concentration of 10 µM, isopulegol derivative 2i containing 3-bromothiophene substituent inhibited FAAH activity with an IC50 value of 7.6 µM. Thus, this compound may increase endocannabinoid system activity.

Keywords

CB1 CB2 Anandamide Fatty acid amide hydrolase (FAAH) Monoacylglycerol lipase (MAGL) Isopulegol Aldehyde 

Notes

Acknowledgements

Synthetic part of this work was supported by Russian Science Foundation (grant 15-13-00017). Authors would like to acknowledge the Multi-Access Chemical Service Center SB RAS for spectral and analytical measurements. AC thanks Prof. Juerg Gertsch for the continuous support on his research activity and inspiring discussions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2294_MOESM1_ESM.pdf (2.2 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Nikolai S. Li-Zhulanov
    • 1
    • 2
  • Irina V. Il’ina
    • 1
    • 2
  • Andrea Chicca
    • 3
  • Patricia Schenker
    • 3
  • Oksana S. Patrusheva
    • 1
  • Ekaterina V. Nazimova
    • 1
  • Dina V. Korchagina
    • 1
  • Mikhail Krasavin
    • 4
  • Konstantin P. Volcho
    • 1
    • 2
    Email author
  • Nariman F. Salakhutdinov
    • 1
    • 2
  1. 1.Novosibirsk Institute of Organic ChemistryNovosibirskRussian Federation
  2. 2.Novosibirsk State UniversityNovosibirskRussian Federation
  3. 3.Institute of Biochemistry and Molecular Medicine, NCCR TransCureUniversity of BernBernSwitzerland
  4. 4.Saint Petersburg State UniversitySaint PetersburgRussian Federation

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