The Inhibitory Effect of Natural Stilbenes and Their Analogues on Catalytic Activity of Cytochromes P450 Family 1 in Comparison with Other Phenols - Structure and Activity Relationship

Mikstacka, Renata; Dutkiewicz, Zbigniew; Sobiak, Stanisław; Baer‐Dubowska, Wanda

doi:10.5772/27660

Cited by 3 publications

(3 citation statements)

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“…The natural phenolic trans-stilbenes with inhibition against the CYP1 family have also been deemed as a series of potential chemopreventive phytochemicals. 19,20 α-Naphthoflavone (ANF, Figure 2), a synthetic flavonoid, is recognized as a strong inhibitor of the CYP1B1 enzyme and has been extensively utilized in the characterization of the CYP1B1mediated specific metabolic reaction. 21 inhibition of 7-ethoxyresorufin O-deethylation (EROD) activity using recombinant human CYP1 enzymes expressed in E. coli membranes.…”

Section: ■ Introductionmentioning

confidence: 99%

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Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

et al. 2015

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CYP1B1 is recognized as a new target in cancer prevention and therapy. Taking α-naphthoflavone as a lead, a series of 6,7,10-trimethoxy-α-naphthoflavones (4a-o) were synthesized and evaluated for their inhibitory potency against CYP1B1 and selectivity over CYP1A1 and 1A2. SAR analysis indicated that introducing methoxy groups at C(6), C(7), and C(10) on the naphthalene part and a fluoro atom at C(3') on the B-ring, could sharply increase the efficiency toward CYP1B1 inhibition. Among the prepared derivatives, compound 4c is the most potent and selective CYP1B1 inhibitor ever reported. More effort was taken to acquire water-soluble α-naphthoflavone derivatives for further cell-based study of overcoming anticancer drug-resistance. Finally, we obtained water-soluble naphthoflavone (11f) which could obviously eliminate the docetaxel-resistance caused by the enhanced expression of CYP1B1 in MCF-7/1B1 cells. It could be envisaged that the discovery of new α-naphthoflavones as CYP1B1 inhibitors is clinically important for overcoming CYP1B1-mediated drug-resistance in cancer therapeutics.

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Section: ■ Introductionmentioning

confidence: 99%

“…The inhibition of CYP1 enzymes has been considered as one of the mechanisms by which these natural products exert their chemoprevention activity. The natural phenolic trans -stilbenes with inhibition against the CYP1 family have also been deemed as a series of potential chemopreventive phytochemicals. , …”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

et al. 2015

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“…The fully methylated compound 2 , while less genotoxic than resveratrol, has been shown to be an ineffective antioxidant against free radicals (21,43,47,48). Methylation of the para ‐hydroxy group has been reported to enhance the ability of 2 and 4 to inhibit cytochrome P450 (49,50). Compound 5 has also been reported to exhibit antioxidant activity as a free radical scavenger and in its ability to reduce lipid peroxidation (51–54).…”

Section: Introductionmentioning

confidence: 99%

Singlet Oxygen Quenching by Resveratrol Derivatives^†

Monsour

Tadle

Tafolla‐Aguirre

et al. 2022

Photochem & Photobiology

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We investigated the singlet oxygen quenching ability of several derivatives of trans-resveratrol which have been reported to have significant antioxidant ability, including photoprotective activity. We measured the total rate constants of singlet oxygen removal (k T ) by the methylated resveratrol derivative 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene, and the partially methylated resveratrol derivatives 4-. A protic solvent system results in higher k T values, except for the completely methylated derivative. We also investigated the ability of transresveratrol to directly act as a photosensitizer (rather than via secondary photoproducts resulting from other primary photochemical reactions) for the production of singlet oxygen but found that neither resveratrol nor any of its derivatives are able to do so. We then studied the chemical reactions of the methylated derivative with singlet oxygen. The main pathway consists of a [4 + 2] cycloaddition reaction involving the trans-double bond and the para-substituted benzene ring similar to what has been observed for trans-resveratrol. Unlike trans-resveratrol, the primary singlet oxygen product undergoes a second [4 + 2] cycloaddition with singlet oxygen leading to the formation of diendoperoxides. A second reactivity pathway for both trans-resveratrol and the methylated derivative leads to the formation of aldehydes via cleavage of a transient dioxetane.

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The Activation of Procarcinogens by CYP1A1/1B1 and Related Chemo-Preventive Agents: A Review

Cui

Jia

2021

CCDT

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: CYP1A1 and CYP1B1 are extrahepatic P450 family members involved in the metabolism of procarcinogens, such as PAHs, heterocyclic amines and halogen-containing organic compounds. CYP1A1/1B1 also participate in the metabolism of endogenous 17-β-estradiol, producing estradiol hydroquinones which are the intermediates of carcinogenic semiquinones and quinones. CYP1A1 and CYP1B1 proteins share approximately half amino acid sequence identity but differ in crystal structures. As a result, CYP1A1 and CYP1B1 have different substrate specificity to chemical procarcinogens. This review will introduce the general molecular biology knowledge of CYP1A1/1B1 and the metabolic processes of procarcinogens regulated by these two enzymes. Over the last four decades, a variety of natural products and synthetic compounds which interact with CYP1A1/1B1 have been identified as effective chemo-preventive agents against chemical carcinogenesis. These compounds are mainly classified as, indirect or direct CYP1A1/1B1 inhibitors based on their distinct mechanisms. Indirect CYP1A1/1B1 inhibitors generally impede the transcription and translation of CYP1A1/1B1 genes or interfere the translocation of aryl hydrocarbon receptor (AHR) from the cytosolic domain to the nucleus. On the other hand, direct inhibitors inhibit the catalytic activities of CYP1A1/1B1. Based on the structural features, the indirect inhibitors can be categorized into the following groups: flavonoids, alkaloids and synthetic aromatics whereas the direct inhibitors can be categorized into flavonoids, coumarins, stilbenes, sulfur containing isothiocyanates and synthetic aromatics. This review will summarize the in vitro and in vivo activities of these chemo-preventive agents, their working mechanisms, and related SARs. This will provide a better understanding of the molecular mechanism of CYP1 mediated carcinogenesis and will also give great implications for the discovery of novel chemo-preventive agents in the near future.

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The Inhibitory Effect of Natural Stilbenes and Their Analogues on Catalytic Activity of Cytochromes P450 Family 1 in Comparison with Other Phenols - Structure and Activity Relationship

Cited by 3 publications

References 68 publications

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

Singlet Oxygen Quenching by Resveratrol Derivatives^†

The Activation of Procarcinogens by CYP1A1/1B1 and Related Chemo-Preventive Agents: A Review

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The Inhibitory Effect of Natural Stilbenes and Their Analogues on Catalytic Activity of Cytochromes P450 Family 1 in Comparison with Other Phenols - Structure and Activity Relationship

Cited by 3 publications

References 68 publications

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

Singlet Oxygen Quenching by Resveratrol Derivatives†

The Activation of Procarcinogens by CYP1A1/1B1 and Related Chemo-Preventive Agents: A Review

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Singlet Oxygen Quenching by Resveratrol Derivatives^†