Effect of chiral polyhydrochromenes on cannabinoid system

Effect of chiral polyhydrochromenes on cannabinoid system Full article

Journal

Medicinal Chemistry Research
ISSN: 1054-2523 , E-ISSN: 1554-8120

Output data

Year: 2019, Volume: 28, Number: 4, Pages: 450-464 Pages count : 15 DOI: 10.1007/s00044-019-02294-9

Tags

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

Authors

Li-Zhulanov Nikolai S. ^1,2 , Il'ina Irina V. ^1,2 , Chicca Andrea ³ , Schenker Patricia ³ , Patrusheva Oksana S. ¹ , Nazimova Ekaterina V. ¹ , Korchagina Dina V. ¹ , Krasavin Mikhail ⁴ , Volcho Konstantin P. ^1,2 , Salakhutdinov Nariman F. ^1,2

Affiliations

1	(Данные Web of science) Novosibirsk Organ Chem Inst, Lavrentjev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Pirogova St 1, Novosibirsk 630090, Russia
3	(Данные Web of science) Univ Bern, NCCR TransCure, Inst Biochem & Mol Med, Buhlstr 28, CH-3012 Bern, Switzerland
4	(Данные Web of science) St Petersburg State Univ, St Petersburg 199034, Russia

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 mu M, isopulegol derivative 2i containing 3-bromothiophene substituent inhibited FAAH activity with an IC50 value of 7.6 mu M. Thus, this compound may increase endocannabinoid system activity.

Li-Zhulanov N.S. , Il'ina I.V. , Chicca A. , Schenker P. , Patrusheva O.S. , Nazimova E.V. , Korchagina D.V. , Krasavin M. , Volcho K.P. , Salakhutdinov N.F.
Effect of chiral polyhydrochromenes on cannabinoid system
Medicinal Chemistry Research. 2019. V.28. N4. P.450-464. DOI: 10.1007/s00044-019-02294-9 WOS Scopus РИНЦ

Published online:	Feb 1, 2019
Published print:	Apr 1, 2019

Web of science	WOS:000462753900003
Scopus	2-s2.0-85061005323
Elibrary	38643899
OpenAlex	W2912773439