Synthesis of 8-geranyloxypsoralen analogues and their evaluation as inhibitors of CYP3A4

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

doi:10.1016/j.bmc.2006.01.046

Cited by 36 publications

(25 citation statements)

References 21 publications

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“…It has been reported that furanocoumarin dimers, possibly derived from the geranyloxy monomer (6Ј,7Ј-DHB), function as potent and selective inhibitors of CYP3A4. 8,9,28,29) Inhibitory effects for the relative yield of each fruit is also interesting to clarify the practical influence of citrus fruits on CYP activity, although the immature fruits were used in this study. In Table 2, evaluated IC 50 (mg fruits/ml) for CYP showed the relatively strong inhibitory effects of C. paradisi.…”

Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of 12 Immature Citrus Fruit Extracts for the Inhibition of Cytochrome P450 Isoform Activities

Fujita

Kawase

Niwa

et al. 2008

Biological & Pharmaceutical Bulletin

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In a previous study we found that 50% ethanol extracts of immature fruits of Citrus unshiu (satsuma mandarin) have anti-allergic effects against the Type I, II and IV allergic reactions. However, many adverse interactions between citrus fruit, especially grapefruit juice, and drugs have been reported due to the inhibition of cytochrome P450 (CYP) activities. The purpose of this study was to examine the competitive inhibitory effects of extracts from immature citrus fruit on CYP activity. Extracts were prepared from 12 citrus species or cultivars, and were tested against three kinds of major CYPs, CYP2C9, CYP2D6 and CYP3A4, in human liver microsomes. We also estimated the amounts of flavonoids (narirutin, hesperidin, naringin and neohesperidin) and furanocoumarins (bergapten, 6,7-dihydroxybergamottin and bergamottin) in each extract using HPLC. Citrus paradisi (grapefruit) showed the greatest inhibition of CYP activities, while Citrus unshiu which has an antiallergic effect, showed relatively weak inhibitory effects. Extracts having relatively strong inhibitory effects for CYP3A4 tended to contain higher amounts of naringin, bergamottin and 6,7-dihydroxybergamottin. These results, providing comparative information on the inhibitory effects of citrus extracts on CYP isoforms, suggest that citrus extracts containing high levels of narirutin and hesperidin and lower levels of furanocoumarins such as C. unshiu are favorable as antiallergic functional ingredients.

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Section: Discussionmentioning

confidence: 99%

Comparative Evaluation of 12 Immature Citrus Fruit Extracts for the Inhibition of Cytochrome P450 Isoform Activities

Fujita

Kawase

Niwa

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Reduction of 3 and 2 with palladium acetate, triethyl amine, and formic acid20 afforded 54 and 55 , respectively. Compound 58 was obtained from 56 by using esterification21 and Heck reactions 22…”

Section: Chemistrymentioning

confidence: 99%

Antitumor Agents. 272. Structure−Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogues

et al. 2010

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Neo-tanshinlactone (1) and its previously reported analogs, such as 2, are potent and selective in vitro anti-breast cancer agents. The synthetic pathway to 2 was optimized from seven to five steps, with a better overall yield. Structure-activity relationships studies on these compounds revealed some key molecular determinants for this family of anti-breast agents. Several derivatives (19-21 and 24) exerted potent and selective anti-breast cancer activity with IC 50 values of 0.3, 0.2, 0.1 and 0.1 μg/ mL, respectively, against the ZR-75-1 cell lines. Compound 24 was two-to three-fold more potent than 1 against SK-BR-3 and ZR-75-1. Importantly, 21 exhibited high selectivity; it was 23 times more active against ZR-75-1 than MCF-7. Compound 20 had an approximately 12-fold ratio of SK-BR-3/MCF-7 selectivity. In addition, analog 2 showed potent activity against a ZR-75-1 xenograft model, but not PC-3 and MDA-MB-231 xenografts, as well as high selectivity against breast cancer cell line compared with normal breast tissue-derived cell lines. Further development of lead compounds 19-21 and 24 as clinical trial candidates is warranted.

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“…For example, CYP3A4 has specific inhibitory effects on bergamottin, the major furanocoumarin in fresh grapefruit juice. 23,24) To estimate the inhibitory effect of atromentic acid (1), variegatic acid (2), and xerocomic acid (3) on these CYP enzymes, in vitro inhibition experiments were performed with five positive controls. The results indicated that variegatic acid (2) and xerocomic acid (3) strongly inhibited all CYP isozyme activities (Table 1).…”

Section: Discussionmentioning

confidence: 99%

In VitroInhibitory Effects of Pulvinic Acid Derivatives Isolated from Chinese Edible Mushrooms,Boletus calopusandSuillus bovinus, on Cytochrome P450 Activity

Huang¹,

Onose²,

Abe³

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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Increasing attention has been focused on food-drug interactions. We have investigated the inhibitory effect of Chinese edible mushrooms, Boletus calopus and Suillus bovinus, on cytochrome P450 (CYP) 1A2, 2C9, 2D6, and 3A4, the main drug-metabolizing enzymes. Three pulvinic acid derivatives, atromentic acid (1), variegatic acid (2), and xerocomic acid (3), isolated from Boletus calopus and Suillus bovinus, revealed nonspecific inhibitory effects on all four CYPs. Using these compounds, the maximum IC50 values obtained with CYP3A4 in vitro were atromentic acid (1), 65.1+/-3.9 microM; variegatic acid (2), 2.2+/-0.1 microM; and xerocomic acid (3), 2.4+/-0.1 microM. Variegatic acid (2) and xerocomic acid (3) were effective inhibitors, comparable to cimetidine, dicoumarol, erythromycin, safrole, and uniconazole. Variegatic acid (2) and xerocomic acid (3) efficiently reduced ferryl myoglobin in CYPs. Reduction of ferryl heme to ferric heme is likely the mechanism of the nonspecific inhibitory effects of these compounds on CYPs.

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Synthesis of 8-geranyloxypsoralen analogues and their evaluation as inhibitors of CYP3A4

Cited by 36 publications

References 21 publications

Comparative Evaluation of 12 Immature Citrus Fruit Extracts for the Inhibition of Cytochrome P450 Isoform Activities

Comparative Evaluation of 12 Immature Citrus Fruit Extracts for the Inhibition of Cytochrome P450 Isoform Activities

Antitumor Agents. 272. Structure−Activity Relationships and In Vivo Selective Anti-Breast Cancer Activity of Novel Neo-tanshinlactone Analogues

In VitroInhibitory Effects of Pulvinic Acid Derivatives Isolated from Chinese Edible Mushrooms,Boletus calopusandSuillus bovinus, on Cytochrome P450 Activity

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