Research output: Contribution to journal › Article › peer-review
Effect of chiral polyhydrochromenes on cannabinoid system. / Li-Zhulanov, Nikolai S.; Il’ina, Irina V.; Chicca, Andrea et al.
In: Medicinal Chemistry Research, Vol. 28, No. 4, 04.2019, p. 450-464.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Effect of chiral polyhydrochromenes on cannabinoid system
AU - Li-Zhulanov, Nikolai S.
AU - Il’ina, Irina V.
AU - Chicca, Andrea
AU - Schenker, Patricia
AU - Patrusheva, Oksana S.
AU - Nazimova, Ekaterina V.
AU - Korchagina, Dina V.
AU - Krasavin, Mikhail
AU - Volcho, Konstantin P.
AU - Salakhutdinov, Nariman F.
N1 - Publisher Copyright: © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - Aldehyde
KW - Anandamide
KW - CB
KW - Fatty acid amide hydrolase (FAAH)
KW - Isopulegol
KW - Monoacylglycerol lipase (MAGL)
KW - METHOXY GROUPS
KW - OCTAHYDRO-2H-CHROMEN-4-OL
KW - RECEPTOR
KW - ISOPULEGOL
KW - MODEL
KW - CB2
KW - CB1
KW - INHIBITION
KW - ACID AMIDE HYDROLASE
KW - VANILLIN
KW - POTENT ANALGESIC ACTIVITY
KW - CATALYZED PRINS
UR - http://www.scopus.com/inward/record.url?scp=85061005323&partnerID=8YFLogxK
U2 - 10.1007/s00044-019-02294-9
DO - 10.1007/s00044-019-02294-9
M3 - Article
AN - SCOPUS:85061005323
VL - 28
SP - 450
EP - 464
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
SN - 1054-2523
IS - 4
ER -
ID: 18487363