Structural Requirements for Potent Direct Inhibition of Human Cytochrome P450 1A1 by Cannabidiol: Role of Pentylresorcinol Moiety
スポンサーリンク
概要
- 論文の詳細を見る
Our recent work has shown that cannabidiol (CBD) exhibits the most potent direct inhibition of human cytochrome P450 1A1 (CYP1A1) among the CYP enzymes examined. However, the mechanism underlying this CBD inhibition remains to be clarified. Thus, to elucidate the structural requirements for the potent inhibition by CBD, the effects of CBD and its structurally related compounds on CYP1A1 activity were investigated with recombinant human CYP1A1. Olivetol, which corresponds to the pentylresorcinol moiety of CBD, inhibited the 7-ethoxyresorufin O-deethylase activity of CYP1A1; its inhibitory effect (IC50=13.8 µ<span style="font-variant: small-caps;">M</span>) was less potent than that of CBD (IC50=0.355 µ<span style="font-variant: small-caps;">M</span>). In contrast, d-limonene, which corresponds to the terpene moiety of CBD, only slightly inhibited CYP1A1 activity. CBD-2′-monomethyl ether (CBDM) and CBD-2′,6′-dimethyl ether inhibited CYP1A1 activity with IC50 values of 4.07 and 23.0 µ<span style="font-variant: small-caps;">M</span>, respectively, indicating that their inhibitory effects attenuated depending on the level of methylation on the free phenolic hydroxyl groups in the pentylresorcinol moiety of CBD. Cannabidivarin inhibited CYP1A1 activity, although its inhibitory potency (IC50=1.85 µ<span style="font-variant: small-caps;">M</span>) was lower than that of CBD. The inhibitory effects of Δ9-tetrahydrocannabinol and cannabielsoin (IC50s ≈10 µ<span style="font-variant: small-caps;">M</span>), which contain a free phenolic hydroxyl group and are structurally constrained, were less potent than that of CBDM, which contains a free phenolic hydroxyl group and is rotatable between pentylresorcinol and terpene moieties. These results suggest that the pentylresorcinol structure in CBD may have structurally important roles in direct CYP1A1 inhibition, although the whole structure of CBD is required for overall inhibition.
著者
-
Watanabe Kazuhito
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
-
Kushihara Mika
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
-
Yamaori Satoshi
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
-
Watanabe Kazuhito
Department Of Chemistry And Chemical Engineering Faculty Of Engineering Yamagata University
-
Narimatsu Shizuo
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
-
Yamamoto Ikuo
Department Of Bioapplied Chemistry Faculty Of Engineering Osaka City University
-
Katsu Takashi
Department of Biophysical Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
-
Okushima Yoshimi
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University
-
Masuda Kazufumi
Department of Physical Chemistry, Graduate School of Clinical Pharmacy, Shujitsu University
-
Narimatsu Shizuo
Department of Health Chemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
関連論文
- Effect of Psychotropic Drugs on the 21-Hydroxylation of Neurosteroids, Progesterone and Allopregnanolone, Catalyzed by Rat CYP2D4 and Human CYP2D6 in the Brain(Biochemistry)
- Differential Expression of Dipeptidyl Peptidase IV (CD26)and Thyroid Peroxidase in Neoplastic Thyroid Tissues
- Butyrylcholinesterase and Erythrocyte Sulfhydryl-dependent Enzyme Hydrolyze Gabexate in Human Blood
- Involvement of Human Blood Arylesterases and Liver Microsomal Carboxylesterases in Nafamostat Hydrolysis
- P2-18 Golgi retention mechanism of CALNUC : NH2-terminal proline plays an essential role for retention
- Effect of Several Cellulosic Binders on Particle Size Distribution of Granules Prepared by a High-Speed Mixer
- Hepatic Metabolism of Methyl Anthranilate and Methyl N-Methylanthranilate as Food Flavoring Agents in Relation to Allergenicity in the Guinea Pig
- Stereospecific and Regioselective Hydrolysis of Cannabinoid Esters by ES46.5K, an Esterase from Mouse Hepatic Microsomes, and Its Differences from Carboxylesterases of Rabbit and Porcine Liver(Biochemistry)
- In Vitro Inhibitory Effects of Cannabinoids on Progesterone 17α-Hydroxylase Activity in Rat Testis Microsomes
- Synthesis of N^3-Substituted Uridine and Related Pyrimidine Nucleosides and Their Antinociceptive Effects in Mice
- Major Cytochrome P450 Enzymes Responsible for Microsomal Aldehyde Oxygenation of 11-Oxo-〓^8-tetrahydrocannabinol and 9-Anthraldehyde in Human Liver
- Skin Reaction Induced by Aldehydes for Food Flavoring Agents
- Possible Existence of a Novel Receptor for Uridine Analogues in the Central Nervous System Using Two Isomers, N^3-(S)-(+)-and N^3-(R)-(-)-α-Hydroxy-β-phenethyluridines
- Hypnotic Action of N^3-Substituted Arabinofuranosyluracils on Mice
- Cross-Reactivity of Various Tetrahydrocannabinol Metabolites with a Monoclonal Antibody against Tetrahydrocannabinolic Acid
- A Carbonyl Reductase-Catalyzing Reduction of N^3-Phenacyluridine in Rabbit Liver
- Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives.
- Characterization of Microsomal Alcohol Oxygenase Catalyzing the Oxidation of 7-Hydroxy-Δ^8-tetrahydrocannabinol to 7-Oxo-Δ^8-tetrahydrocannabinol in Rat Liver
- Synthesis and Central Nervous System Depressant Effects of N^3-Substituted 2', 3'-O-Isopropylideneuridines
- Synthesis and Pharmacological Evaluation in Mice of Halogenated Cannabidiol Derivatives
- Pharmacologica Efects in Mice of Anandamide and Its Related Fatty Acid Ethanolamides, and Enhancement of Cataleptogenic Effect of Anandamide by Phenylmethylsulfonyl Fluoride
- Effects of Heavy Oil from the Nakhodka on Hepatic and Pulmonary Enzymes of Mice(PROCEEDINGS OF 24TH SYMPOSIUM ON TOXICOLOGY AND ENVIRONMENTAL HEALTH)
- Synthesis and Pharmacological Activities in Mice of Halogenated Δ^9-Tetrahydrocannabinol Derivatives
- Effective NADH-Dependent Oxidation of 7β-Hydroxy-Δ^8-tetrahydrocannabinol to the Corresponding Ketone by Japanese Monkey Hepatic Microsomes(Toxicology)
- Monkey Hepatic Microsomal Alcohol Oxygenase: Purification and Characterization of a Cytochrome P450 Enzyme Catalyzing the Stereoselective Oxidation of 7α-and 7β-Hydroxy-Δ^8-tetrahydrocannabinol to 7-Oxo-Δ^8-tetrahydrocannabinol
- A Cytochrome P450 Enzyme Responsible for the Carbon Monoxide Formation by Cannabidiol in Mouse Hepatic Microsomes.
- Inhibition of Mouse Hepatic Glutathione S-Transferase by Δ^8-Tetrahydrocannabinol p-Quinone and Cannabidiol Hydroxy-quinone.
- Microsomal Aldehyde Oxygenase (MALDO) for Tolualdehydes, Active Metabolites of Xylenes, in the Mouse Liver and Lung
- "B-4 Hydrolysis of Xenobiotics by ES46.5K, a Novel Esterase from Mouse Liver Microsomes
- Stereoselectivity in Bunitrolol 4-Hydroxylation in Liver Microsomes from Marmosets and Japanese Monkeys
- Microsomal Aldehyde Oxygenase (MALDO): Purification and Characterization of a Cytochrome P450 Isozyme Responsible for Oxidation of 9-Anthraldehyed to 9-Anthracenecarboxylic Acid in Monkey Liver
- Determination of Heavy Metal Contents in Human Gallstones Using X-Ray Fluorescence Spectrometry (Regular Presentations) (Proceedings of the 15 th Symposium on Environmental Pollutants and Toxicology)
- Determination of Metal Contents in River Sediment Near a Closed Mine by X-ray Fluorescence Spectrometry (Proceedings of the 14th Symposium on Environmental Pollutants and Toxicology)
- Determination of Metal Contents in Biological and Environmental Materials by Energy-Dispersive X-Ray Fluorescence Analysis
- MECHANISM OF SLEEP-PROLONGATING EFFECT OF Δ^8-TETRAHYDROCANNABINOL (Δ^8-THC) AND ITS METABOLITES
- Critical Anomaly of the Third-Order Elastic Constants in CsPbCl_3
- Mechanism of Inhibitory Effects of Cannabidiol and Cannabidiol Hydroxy-quinone on the Hepatic Microsomal Drug-Metabolizing Enzymes in Mice (Proceedings of the 23rd Symposium on Toxicology and Environmental Health)
- Involvement of a Novel Mouse Hepatic Microsomal Esterase, ES46.5K, in the Hydrolysis of Phthalate Esters
- Mechanism of Hepatic Microsomal Oxidation of 11-Hydroxy-Δ^8-tetra-hydrocannabinol to 11-Oxo-Δ^8-tetrahydrocannabinol. Evidence for Hydration of the Aldehyde Formed
- INTERACTION OF CANNABINOIDS WITH HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
- PURIFICATION AND CHARACTERIZATION OF MOUSE HEPATIC MICROSOMAL ALDEHYDE OXYGENASE
- MECHANISM OF CANNABIELSOIN FORMATION FROM CANNABIDIOL, ONE OF THE MAJOR CMPONENTS OF MARIHUANA
- CYTOCHROME P450 ISOZYMES INVOLVED IN METABOLIC ACTIVATION OF Δ^9-TETRAHYDROCANNABINOL BY RAT LIVER MICROSOMES
- Mechanism of Biological Formation of Cannabielsoin from Cannabidiol in the Guinea-Pig, Mouse, Rat and Rabbit
- HEPATIC MICROSOMAL OXYGENATION OF METHYL GROUP TO CARBOXYLIC ACID IN XENOBIOTICS : METABOLISM OF Δ^8-TETRAHYDROCANNABINOL AT THE 11-POSITION
- Identification of Cannabielsoin, a New Metabolite of Cannabidiol Formed by Guinea-Pig Hepatic Microsomal Enzymes, and Its Pharmacological Activity in Mice
- METABOLIC DISPOSITION OF 8α, 9α-AND 8β, 9β-EPOXYHEXAHYDROCANNABINOLS IN THE MOUSE
- DIFFERENCE IN EPOXIDES FORMATION AND THEIR FURTHER METABOLISM BETWEEN Δ^9 -AND Δ^8-TETRAHYDROCANNABINOLS BY HUMAN LIVER MICROSOMES
- The Synthesis of Isoquinoline Alkaloid and Its Related Compounds Using Alanine Derivatives as Chiral Auxiliaries
- c-Kit Proto-oncogene Is More Likely to Lose Expression in Differentiated Thyroid Carcinoma Than Three Thyroid-specific Genes : Thyroid Peroxidase, Thyroglobulin, and Thyroid Stimulating Hormone Receptor
- Compertitive Inhibition of Δ^8-Tetrahydrocannabinol and Its Active Metabolites for Cannabinoid Receptor Binding
- Anandamide, an Endogenous Cannabinoid Receptor Ligand, Also Interacts with 5-Hydroxytryptamine (5-HT) Receptor
- Synthesis and Hypnotic Activities of 4-Thio Analogues of N^3-Substituted Uridines
- Establishment by Adriamycin Exposure of Multidrug-resistant Rat Ascites Hepatoma AH130 Cells Showing Low DT-diaphorase Activity and High Cross Resistance to Mitomycins
- Inhibition of P-Glycoprotein-Dependent Multidrug Resistance by an Isoquinolinesulfonamide Compound H-87 in Rat Ascites Hepatoma AH66 Cells
- Biphasic Kinetics of Imipramine N-Oxidation in Rat Brain Microsomes
- A Novel Series of Thromboxane A_2 Synthetase Inhibitors with Free Radical Scavenging and Anti-peroxidative Activities
- Bioavailable Acyl-CoA : Cholesterol Acyltransferase Inhibitor with Anti-peroxidative Activity : Synthesis and Biological Activity of Novel Indolinyl Amide and Urea Derivatives
- Studies on the Constituents of Broussonetia Species. V. Two New Pyrrolidine Alkaloids, Broussonetines K and L, as Inhibitors of Glycosidase, from Broussonetia Kazinoki SIEB.
- Facile Formation of Chiral Calixarene Analogs Incorporating Cystine Peptide into the Macrocyclic Ring.
- Reductive Dimerization of Alkylidenemalonates Using Samarium(II) Diiodide and ^1H-NMR Behavior of the Dimers, 2,3-Diaryl-1,1,4,4-butanetetracarboxylates
- Contribution of Flavin-Containing Monooxygenase and Cytochrome P450 to Imipramine N-Oxidation in Rat Hepatic Microsomes
- STRUCTURE-ACTIVITY RELATIONSHIP OF URIDINE DERIVATIVES FOR HYPNOTIC ACTIVITY
- Accurate Measurements and Determination of the Magnetic Anisotropies of Several Manganese Crystals
- INHIBITORY EFFECT OF CANNABIDIOL ON THE HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
- Biquadratic Exchange Effect on the Magnetic Anisotropy in a Heisenberg Linear Chain Antiferromagnet [(CH_3)_3NH]MnBr_32H_2O
- EPR g-Shift and Anisotropic Magnetic Susceptibility in K_2MnF_4
- Studies on the Constituents of Broussonetia Species. IV. Two New Pyrrolidinyl Piperidine Alkaloids, Broussonetines I and J, from Broussonetia kazinoki SIEB.
- Studies on the Constituents of Broussonetia Species. III. Two New Pyrrolidine Alkaloids, Broussonetines G and H, as Inhibitors of Glycosidase, from Broussonetia kazinoki SIEB.
- Studies on the Constituents of Broussonetia Species. II. Six New Pyrrolidine Alkaloids, Broussonetine A, B, E, F and Broussonetinine A and B, as Inhibitors of Glycosidases from Broussonetia kazinoki SIEB.
- A pivotal role of IL-12 in T_h 1-dependent mouse liver injury
- Interleukin-12 Augments the Generation of Autologous Tumor-reactive CD8^+ Cytotoxic T Lymphocytes from Tumor-infiltrating Lymphocytes
- Determination of Virial Coefficient of N-isopropylacrylamide Polymer Solution by Light Scattering Measurements
- Brillouin Scattering Study of the Ferroelectric Phase Transition in NH_4LiSO_4
- Fluorometric Determination of Hydrogen Peroxide Based on Formation of Amprochrome
- Rapid Determination of Trace Metals in Foods by Using the Microwave Oven-Digestion Method. II. Determination of Zinc, Copper, Manganese, Lead and Cadmium
- Rapid Determination of Trace Metals in Foods by Using the Microwave Oven-Digestion Method. I. Determination of Arsenic
- Anomalous Temperature Dependence of the Intensity of Brillouin Scattering near the Ferroelectric Phase Transition Point of NH_4LiSO_4
- Cannabidiol-2′,6′-dimethyl Ether as an Effective Protector of 15-Lipoxygenase-Mediated Low-Density Lipoprotein Oxidation in Vitro
- Mechanism of Pulmonary Cytochrome P450 Inactivation by Tolualdehydes, Active Metabolites of Xylenes (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
- Metabolic Reaction of Tolualdehydes by Microsomal Aldehyde Oxygenase (MALDO) in Lung (Proceedings of the 19th Symposium on Toxicology and Environmental Health)
- Diameter and Refractive Index of a Cylindrical Thread Determined by Scattered Light Pattern
- INHIBITION OF ANANDAMIDE AMIDASE ACTIVITY IN MOUSE BRAIN MICROSOMES BY CANNABINOIDS
- Involvement of a Novel Mouse Hepatic Esterase (ES46.5K) in the Hydrolysis of Phthalate Esters (Proceedings of the 21st Symposium on Toxicology and Environmental Health)
- Involvement of Microsomal Aldehyde Oxygenase (MALDO) in the Metabolism of Aliphatic Aldehydes in the Mouse Liver (Proceedings of the 20th Symposium on Toxicology and Environmental Health)
- Studies on Metabolism and Toxicity of Organic Solvents, Toluene and Related Compounds : Metabolism of Benzaldehydes by Microsomal Aldehyde Oxygenase (MALDO) (Proceedings of the 18th Symposium on Toxicology, and Environmental Health)
- 9α, 10α-EPOXYHEXAHYDROCANNABINOL FORMATION FROM Δ^9-TETRAHYDROCANNABINOL BY LIVER MICROSOMES OF PHENOBARBITAL-TREATED MICE AND ITS PHARMACOLOGICAL ACTIVITIES IN MICE
- Light Scattering Study of Condensation of Poly (N-isopropylacrylamide) Chain
- Asymmetric Dielectric Dispersion in a Random Dipole System
- Random Interaction among Dipolar Impurities in Alkali Halide: KI^(NO_2)_x
- Oblique-Antiferromagnetic phase of a Random Magnetic Mixture, CsMn_Co_xCl_32H_2O
- Elastic Softening at the Order-Disorder Phase Transition in a Plastic Crystal RbNO_2
- Magnetic Anisotropy Measurement on CsMnCl_3
- Affine Transformation and Differential Equation to Solve Optimal Moving Directions Across the Sea(Session 1b)
- 1,2-Dotriacontanedioyl-sn-Glycero-3-Phosphocholine : A Cyclic Lipid Used for Phospholipase A_2-Catalvzed Modulation of the Liposome Surface Charge
- Differentiation of Monkey Embryonic Stem Cells to Hepatocytes by Feeder-free Dispersion Culture and Expression Analyses of Cytochrome P450 Enzymes Responsible for Drug Metabolism
- Structural Requirements for Potent Direct Inhibition of Human Cytochrome P450 1A1 by Cannabidiol: Role of Pentylresorcinol Moiety
- The Autoxidation of Phenols Catalyzed by Phthalocyanine-Fe(II) and Salcomine-pyridine
- Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ^9-tetrahydrocannabinol in human breast cancer cells
- Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells