6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2

Kato, Atsushi; Kobayashi, Kaori; Narukawa, Kayo; Minoshima, Yuka; Adachi, Isao; Hirono, Shuichi; Nash, Robert J.

doi:10.1016/j.bmcl.2010.08.038

Cited by 16 publications

(7 citation statements)

References 20 publications

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“…Through Surflex-Dock calculations, the estimated –log 10 K d of each reference molecules was calculated and listed in Table 1 . There existed a good linear correlation between experimental pIC 50 33 34 35 36 and the calculated –log 10 K d (equation 1 , Fig. 6 , details in the Methods), indicating that –log 10 K d obtained from Surflex-Dock calculation was an appropriate theoretical parameter to characterize the enzyme-inhibiting activity in theoretical treatment of these systems.…”

Section: Resultsmentioning

confidence: 84%

How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

Shen

Liu

et al. 2016

Sci Rep

110

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Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer’s disease (AD), including the superoxide anion radical (O2.–)-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2.–-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product.

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Section: Resultsmentioning

confidence: 84%

How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

Shen

Liu

et al. 2016

Sci Rep

110

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“…Since these closely related members of the AKR family are responsible for the reduction of toxic aldehydes, the simultaneous inhibition of ALR1/ALR2 could cause harmful side effects” [ 8 , 38 ]. ALR1 inhibitory activity is expressed as IC 50 values presented together with the calculated selectivity index (Table 1 ), along with the reference compound epalrestat [ 39 , 40 ].…”

Section: Resultsmentioning

confidence: 99%

Non-acidic bifunctional benzothiazole-based thiazolidinones with antimicrobial and aldose reductase inhibitory activity as a promising therapeutic strategy for sepsis

et al. 2021

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Sepsis is a life-threatening disease that affects millions of people worldwide. Microbial infections that lead to sepsis syndrome are associated with an increased production of inflammatory molecules. Aldose reductase has recently emerged as a molecular target that is involved in various inflammatory diseases, including sepsis. Herein, a series of previously synthesized benzothiazole-based thiazolidinones that exhibited strong antibacterial and antifungal activities has been evaluated for inhibition efficacy against aldose reductase and selectivity toward aldehyde reductase under in vitro conditions. The most promising inhibitor 5 was characterized with IC 50 value of 3.99 μM and a moderate selectivity. Molecular docking simulations revealed the binding mode of compounds at the active site of human aldose reductase. Moreover, owning to the absence of an acidic pharmacophore, good membrane permeation of the novel aldose reductase inhibitors was predicted. Excellent “drug-likeness” was assessed for most of the compounds by applying the criteria of Lipinski’s “rule of five”.

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“…Overlapping substrate spectra are considered a major pitfall of many ARIs, as they often inhibit AKR1A1 and AKR1B1 simultaneously, thereby interfering with their central role in detoxification processes. This has raised the demand for selective inhibitors that preferentially bind to AKR1B1 and leave the activity of AKR1A1 unaffected 47–49 .…”

Section: Introductionmentioning

confidence: 99%

The hop-derived compounds xanthohumol, isoxanthohumol and 8-prenylnaringenin are tight-binding inhibitors of human aldo-keto reductases 1B1 and 1B10

Seliger¹,

Misuri

Maser³

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Xanthohumol (XN), a prenylated chalcone unique to hops (Humulus lupulus) and two derived prenylflavanones, isoxanthohumol (IX) and 8-prenylnaringenin (8-PN) gained increasing attention as potential anti-diabetic and cancer preventive compounds. Two enzymes of the aldo-keto reductase (AKR) superfamily are notable pharmacological targets in cancer therapy (AKR1B10) and in the treatment of diabetic complications (AKR1B1). Our results show that XN, IX and 8-PN are potent uncompetitive, tight-binding inhibitors of human aldose reductase AKR1B1 (Ki = 15.08 μM, 0.34 μM, 0.71 μM) and of human AKR1B10 (Ki = 20.11 μM, 2.25 μM, 1.95 μM). The activity of the related enzyme AKR1A1 was left unaffected by all three compounds. This is the first time these three substances have been tested on AKRs. The results of this study may provide a basis for further quantitative structure–activity relationship models and promising scaffolds for future anti-diabetic or carcinopreventive drugs.

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6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2

Cited by 16 publications

References 20 publications

How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies

Non-acidic bifunctional benzothiazole-based thiazolidinones with antimicrobial and aldose reductase inhibitory activity as a promising therapeutic strategy for sepsis

The hop-derived compounds xanthohumol, isoxanthohumol and 8-prenylnaringenin are tight-binding inhibitors of human aldo-keto reductases 1B1 and 1B10

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