Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4

Row, Eleanor C.; Brown, Stuart A.; Stachulski, Andrew V.; Lennard, M. S.

doi:10.1039/b601096b

Cited by 38 publications

(40 citation statements)

References 17 publications

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“…The synthesis of AUR was based on a literature procedure [10], modified as follows. Geranyl chloride (42 g, 0.24 mol), synthesized as reported elsewhere [11], was added to a 2-L round bottom flask along with acetone (800 mL), potassium carbonate (45 g, 0.32 mol), and 7-hydroxycoumarin (35.8 g, 0.22 mol), obtained from Sigma-Aldrich.…”

Section: Methodsmentioning

confidence: 99%

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

et al. 2010

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BackgroundActivation of nuclear factor erythroid 2-related factor (Nrf2), which belongs to the basic leucine zipper transcription factor family, is a strategy for cancer chemopreventive phytochemicals. It is an important regulator of genes induced by oxidative stress, such as glutathione S-transferases, heme oxygenase-1 and peroxiredoxin 1, by activating the antioxidant response element (ARE). We hypothesized that (1) the citrus coumarin auraptene may suppress premalignant mammary lesions via activation of Nrf2/ARE, and (2) that Nrf2 knockout (KO) mice would be more susceptible to mammary carcinogenesis.MethodsPremalignant lesions and mammary carcinomas were induced by medroxyprogesterone acetate and 7,12-dimethylbenz[a]anthracene treatment. The 10-week pre-malignant study was performed in which 8 groups of 10 each female wild-type (WT) and KO mice were fed either control diet or diets containing auraptene (500 ppm). A carcinogenesis study was also conducted in KO vs. WT mice (n = 30-34). Comparisons between groups were evaluated using ANOVA and Kaplan-Meier Survival statistics, and the Mann-Whitney U-test.ResultsAll mice treated with carcinogen exhibited premalignant lesions but there were no differences by genotype or diet. In the KO mice, there was a dramatic increase in mammary carcinoma growth rate, size, and weight. Although there was no difference in overall survival, the KO mice had significantly lower mammary tumor-free survival. Also, in the KO mammary carcinomas, the active forms of NF-κB and β-catenin were increased ~2-fold whereas no differences in oxidized proteins were observed. Many other tumors were observed, including lymphomas. Interestingly, the incidences of lung adenomas in the KO mice were significantly higher than in the WT mice.ConclusionsWe report, for the first time, that there was no apparent difference in the formation of premalignant lesions, but rather, the KO mice exhibited rapid, aggressive mammary carcinoma progression.

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Section: Methodsmentioning

confidence: 99%

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

et al. 2010

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“…We consider that Cou and (or) VO should enhance the analgesic effect of CA is related to the improvement of plasma concentration of dl-THP. 4-and 9-Prenyl furo(3,2-g)benzopyran-7-ones, closely related to furocoumarins of grapefruit juice involved in the modification in the pharmacokinetics of various active principles, through modulation of their metabolism by hepatic cytochrome P450 (Guo et al, 2000;Bellevue et al, 1997;Row et al, 2006). 4-and 9-Prenyl furo(3,2-g)benzopyran-7-ones are also major coumarins of Angelica dahurica, and Cou are involved in the modification in the pharmacokinetics of dl-THP in CA that may be related to these components.…”

Section: Discussionmentioning

confidence: 99%

Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP

Liu

Liang

Zhu

et al. 2010

Journal of Ethnopharmacology

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“…15) On the other hand, BT did not inhibit CYP3A activities in microsomes from humans and rats. 5,16) Furthermore, the uptake experiment of vinblastine by Caco-2 cells revealed that BT has little inhibitory effect on P-glycoprotein unlike BG and DHB.…”

Section: Discussionmentioning

confidence: 99%

The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice

Uesawa

Mohri

2006

Biological & Pharmaceutical Bulletin

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It has been reported that when many types of drugs, including dihydropyridine calcium antagonists, are taken with grapefruit juice (GJ), their concentrations in plasma increases due to their increased bioavailabilities.1,2) Serious adverse effects have been known to result. 3,4) Many patients being treated for chronic diseases are forbidden to drink GJ for the rest of their lives because of the risk of such drug interactions. The drugs interacting with GJ are metabolized by CYP3A enzymes in the small intestine. Furanocoumarin derivatives (FCs), such as bergamottin (BG) and 6Ј,7Ј-dihydroxybergamottin (DHB), in GJ inhibit this process. [5][6][7][8][9][10][11] Therefore, in order to produce GJ that vulnerable patients may drink, it would be useful to remove the interactive components of GJ. This possibility has been little investigated.We recently reported that ultraviolet (UV) irradiation eliminates FCs in GJ.12) Furthermore, GJ that was UV-irradiated for 6 h lost the ability to interact with intraduodenal nifedipine (NFP) in rats. However, this method has the drawback that, over the long term, toxic substances might be formed in UV-irradiated GJ. Paine et al. have reported a method of removing BG and DHB from GJ by means of a pilot-scale citrus-debittering system consisting of three ultrafiltration cartridges and a styrene divinyl benzene absorption resin system.13) This equipment is complicated and probably expensive. In the present study, we found that BG and DHB in GJ were unstable at high temperatures. It is therefore proposed that the heat treatment of GJ might serve as the basis for the removal of interactive FCs and thus the elimination of potential drug interactions. Furthermore, GJ samples after heat treatment under various conditions, including various concentrations of FCs, are still useful for elucidating the functions of FCs in drug interactions. With such a background, we studied the effect of incubation at various temperatures on the concentrations of FCs in GJ, and the actions of the GJ samples on the drug interactions in vitro and in vivo. MATERIALS AND METHODSAll handling procedures involving NFP and nitrendipine were performed under subdued light.Materials Anthracene [internal standard (IS)] was obtained from Wako Pure Chemical Industries Ltd. (Osaka, Japan). BG and DHB were purchased from Daiichi Pure Chemicals Co., Ltd. (Tokyo, Japan). Bergaptol (BT) was obtained from Funakoshi Co., Ltd. (Tokyo, Japan). NFP was purchased from Wako Pure Chemical Industries. Nitrendipine [internal standard (IS2)] was obtained from Yoshitomi Pharmaceutical Industries, Ltd. (Osaka, Japan). Testosterone was obtained from Nacalai Tesque, Inc. (Kyoto, Japan). 6b-Hydroxytestosterone and corticosterone [internal standard (IS3)] were purchased from Daiichi Pure Chemicals and Wako Pure Chemical Industries, respectively. Pooled human hepatic microsomes were obtained from BD Biosciences (San Jose, CA, U.S.A.). Methanol, acetonitrile, and phosphoric acid of HPLC grade were used (Wako). All other chemicals were of reagent g...

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Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4

Cited by 38 publications

References 17 publications

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene

Correlation between synergistic action of Radix Angelica dahurica extracts on analgesic effects of Corydalis alkaloid and plasma concentration of dl-THP

The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice

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