Role of human flavin-containing monooxygenase (FMO) 5 in the metabolism of nabumetone: Baeyer–Villiger oxidation in the activation of the intermediate metabolite, 3-hydroxy nabumetone, to the active metabolite, 6-methoxy-2-naphthylacetic acid
            <i>in vitro</i>

Matsumoto, Kaori; Hasegawa, Tetsuya; Ohara, Kosuke; Kamei, Tomoyo; Koyanagi, Jyunichi; Akimoto, Masayuki

doi:10.1080/00498254.2020.1843089

Cited by 12 publications

(4 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, raloxifene and menadione are well-known specifi c inhibitors of AO. Although MONAL-62, an aldehyde analog, is an aldehyde dehydrogenase substrate, it also acts as an AO inhibitor without any cofactors (29). MONAL-62 was selected because of its inhibitory effects, even on AO substrates, which are not suppressed by raloxifene or menadione (29).…”

Section: Discussionmentioning

confidence: 99%

“…Although MONAL-62, an aldehyde analog, is an aldehyde dehydrogenase substrate, it also acts as an AO inhibitor without any cofactors (29). MONAL-62 was selected because of its inhibitory effects, even on AO substrates, which are not suppressed by raloxifene or menadione (29). MONAL-62 is a structurally similar compound of metabolite generated from nabumetone, an anti-infl ammatory drug, by fl avin monooxygenase 5 (FMO5).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Weak Inhibitory Effects of Anthocyanins on Human Aldehyde Oxidase Activity: An In Vitro Study

SHIBATA

Matsumoto

Hasegawa

et al. 2023

J Nutr Sci Vitaminol

Self Cite

View full text Add to dashboard Cite

Aldehyde oxidase (AO) plays an important role in the metabolism of antitumor and antiviral drugs, including methotrexate, favipiravir, and acyclovir. The consumption of blueberry fruits or their extracts, which contain large amounts of anthocyanins, has recently increased. The intake of large amounts of anthocyanins occurs through the frequent consumption of blueberries or their functional foods, which may result in unwanted interactions between anthocyanins and medicinal drugs. Therefore, the present study examined the inhibition of AO by anthocyanins, anthocyanidins, and blueberry extracts in human liver cytosol using a HPLC assay. A comparison of the 50% inhibitory concentration (IC50) values of the test compounds showed that anthocyanidins slightly suppressed AO activity, whereas the inhibitory effects of anthocyanins and blueberry extracts were negligible. The inhibitory activities of the anthocyanins tested were approximately 60-to 130-fold weaker than that of the positive control menadione and were almost negligible. Furthermore, they were approximately 2,000-fold less potent than that of raloxifene, a typical AO inhibitor, and, thus, unlikely to interfere with drug metabolism by AO. In addition, since the plasma concentrations of anthocyanins after their administration were generally lower than the IC50 level, the inhibition of AO substrate metabolism by anthocyanins does not appear to be severe.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Weak Inhibitory Effects of Anthocyanins on Human Aldehyde Oxidase Activity: An In Vitro Study

SHIBATA

Matsumoto

Hasegawa

et al. 2023

J Nutr Sci Vitaminol

Self Cite

View full text Add to dashboard Cite

show abstract

“…15). (Matsumoto et al, 2021) In order to confirm the intermediacy of 6-MN-CHO, the authors performed a trapping experiment by incubating 3-OH-NAB with human FMO5 followed by addition of a fluorescence labelling reagent, 4-(N,N-Dimethyl-amino-sulfonyl)-7-hydrazino-2,1,3-benzoxadiazole (DBD-H). The DBD-H derivative of 3-OH-NAB was detected using an HPLC system coupled to a fluorescence detector.Incorporation of an oxetane moiety has been shown to improve the overall pharmacokinetic as well as physicochemical properties of AZD1979 (Johansson et al, 2016) a melanin-concentrating hormone receptor 1 antagonist.…”

Section: Other Unusual Biotransformation Reactionsmentioning

confidence: 99%

Unusual Biotransformation Reactions of Drugs and Drug Candidates

Isin

2023

Drug Metabolism and Disposition

View full text Add to dashboard Cite

Detailed assessment of the fate of drugs in non-clinical test species and humans is essential to ensure the safety and efficacy of medicines in patients. In this context, biotransformation of drugs and drug candidates has been an area of keen interest over many decades in the pharmaceutical industry as well as academia. Although many of the enzymes and biotransformation pathways involved in the metabolism of xenobiotics and more specifically drugs have been well-characterized, each drug molecule is unique and constitutes specific challenges for the biotransformation scientist. In this mini-review written for the Special Issue on the occasion of the 50 th Anniversary celebration of DMD and to celebrate contributions of Prof. F. Peter Guengerich, one of the pioneers of the drug metabolism field, recently reported "unusual" biotransformation reactions are presented. Scientific and technological advances in the "toolbox" of the biotransformation scientists are summarized. As the pharmaceutical industry continues to explore therapeutic modalities different from the traditional small molecule drugs, the new challenges confronting the biotransformation scientist as well as future opportunities are discussed.

show abstract

“…Extensive research has been conducted to elucidate FMOs biochemical properties, substrate specificities, and functional roles. Among them, FMO5 stands out as it exhibits no activity towards trimethylamine [16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

Mice, rats, and guinea pigs differ in FMOs expression and tissue concentration of TMAO, a gut bacteria-derived biomarker of cardiovascular and metabolic diseases

Maksymiuk,

Szudzik,

Samborowska

et al. 2024

PLoS ONE

View full text Add to dashboard Cite

Introduction Increased plasma trimethylamine oxide (TMAO) is observed in cardiovascular and metabolic diseases, originating from the gut microbiota product, trimethylamine (TMA), via flavin-containing monooxygenases (FMOs)-dependent oxidation. Numerous studies have investigated the association between plasma TMAO and various pathologies, yet limited knowledge exists regarding tissue concentrations of TMAO, TMAO precursors, and interspecies variability. Methods Chromatography coupled with mass spectrometry was employed to evaluate tissue concentrations of TMAO and its precursors in adult male mice, rats, and guinea pigs. FMO mRNA and protein levels were assessed through PCR and Western blot, respectively. Results Plasma TMAO levels were similar among the studied species. However, significant differences in tissue concentrations of TMAO were observed between mice, rats, and guinea pigs. The rat renal medulla exhibited the highest TMAO concentration, while the lowest was found in the mouse liver. Mice demonstrated significantly higher plasma TMA concentrations compared to rats and guinea pigs, with the highest TMA concentration found in the mouse renal medulla and the lowest in the rat lungs. FMO5 exhibited the highest expression in mouse liver, while FMO3 was highly expressed in rats. Guinea pigs displayed low expression of FMOs in this tissue. Conclusion Despite similar plasma TMAO levels, mice, rats, and guinea pigs exhibited significant differences in tissue concentrations of TMA, TMAO, and FMO expression. These interspecies variations should be considered in the design and interpretation of experimental studies. Furthermore, these findings may suggest a diverse importance of the TMAO pathway in the physiology of the evaluated species.

show abstract

Role of human flavin-containing monooxygenase (FMO) 5 in the metabolism of nabumetone: Baeyer–Villiger oxidation in the activation of the intermediate metabolite, 3-hydroxy nabumetone, to the active metabolite, 6-methoxy-2-naphthylacetic acid in vitro

Cited by 12 publications

References 44 publications

Weak Inhibitory Effects of Anthocyanins on Human Aldehyde Oxidase Activity: An In Vitro Study

Weak Inhibitory Effects of Anthocyanins on Human Aldehyde Oxidase Activity: An In Vitro Study

Unusual Biotransformation Reactions of Drugs and Drug Candidates

Mice, rats, and guinea pigs differ in FMOs expression and tissue concentration of TMAO, a gut bacteria-derived biomarker of cardiovascular and metabolic diseases

Contact Info

Product

Resources

About