Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model

Chang, Ken‐Ming; Chen, Huang-Hui; Wang, Tai‐Chi; Chen, I‐Li; Chen, Yu-Tsen; Yang, Shyh-Chyun; Chen, Yeh‐Long; Chang, Hsin-Huei; Huang, Chiung‐Shiann; Chang, Jang‐Yang; Shih, Chuan; Kuo, Ching‐Chuan; Tzeng, Cherng‐Chyi

doi:10.1016/j.ejmech.2015.10.029

Cited by 16 publications

(7 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…182–183 °C; silica gel TLC R f 0.56 (MeOH/DCM 10% v / v ); δ H (400 MHz, DMSO- d 6 ) 4.80 (2H, s), 6.54 (1H, d, J = 9.6 Hz), 7.12 (1H, t , J = 7.4 Hz), 7.36 (4H, m), 7.43 (1H, d, J = 8.7), 7.68 (2H, d, J = 7.4 Hz), 8.07 (1H, d, J = 9.6 Hz), 10.14 (1H, s, exchange with D 2 O, N H ); δ C (100 MHz, DMSO- d 6 ) 68.6, 113.0, 117.6, 118.3, 120.1, 120.6, 120.8, 124.6, 129.7, 139.2, 144.9, 149.1, 155.1, 161.0, 167.1. m / z (ESI positive) (C 17 H 13 NO 4 ) 296.2 [M + H] + . Experimental data are in agreement with those reported in [ 39 ].…”

Section: Methodssupporting

confidence: 92%

“…206–207 °C; silica gel TLC R f 0.86 (MeOH/DCM 10% v / v ); δ H (400 MHz, DMSO- d 6 ) 4.79 (2H, s), 6.52 (1H, d, J = 9.6 Hz), 7.18 (2H, t, J = 8.8), 7.38 (3H, m), 7.68 (2H, m), 8.03 (1H, d, J = 9.6 Hz), 10.22 (1H, s, exchange with D 2 O, N H ); δ C (100 MHz, DMSO- d 6 ) 68.6, 113.1, 116.3 (d, 2 J C-F 22), 117.7, 118.5, 120.2, 121.0, 122.8 (d, 3 J C-F 8), 135.6 (d, 4 J C-F 3), 145.1, 149.3, 155.2, 159.3 (d, 1 J C-F 238.8), 161.2, 167.3. δ F (376 MHz, DMSO- d 6 ) −118.78 (1F, s); m / z (ESI positive) (C 17 H 12 FNO 4 ) 314.2 [M + H] + . Experimental data are in agreement with those reported in [ 39 ].…”

Section: Methodssupporting

confidence: 92%

“…N-(4-Fluorophenyl)-2-((2-oxo-2H-chromen-6-yl)oxy)acetamide ( 8b ) [ 39 ]. Using 3b and 8 as starting materials and the general procedure described above compound 8b was obtained as a white solid in 80% yield; m.p.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX

et al. 2018

View full text Add to dashboard Cite

A series of carboxamide derivatives of 6- and 7-substituted coumarins have been prepared by an original procedure starting from the corresponding 6- or 7-hydroxycoumarins which were alkylated with ethyl iodoacetate, and the obtained ester was converted to the corresponding carboxylic acids which were thereafter reacted with a series of aromatic/aliphatic/heterocyclic amines leading to the desired amides. The new derivatives were investigated as inhibitors of two enzymes, human carbonic anhydrases (hCAs) and soy bean lipoxygenase (LOX). Compounds 4a and 4b were potent LOX inhibitors, whereas many effective hCA IX inhibitors (KIs in the range of 30.2–30.5 nM) were detected in this study. Two compounds, 4b and 5b, showed the phenomenon of dual inhibition. Furthermore, these coumarins did not significantly inhibit the widespread cytosolic isoforms hCA I and II, whereas they were weak hCA IV inhibitors, making them hCA IX-selective inhibitors. As hCA IX and LOX are validated antitumor targets, these results are promising for the investigation of novel drug targets involved in tumorigenesis.

show abstract

Section: Methodssupporting

confidence: 92%

Section: Methodssupporting

confidence: 92%

See 1 more Smart Citation

Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Nrf2 principally regulates transcriptional activation through an antioxidant responsive element (ARE) (24), which is considered to be a cis-acting regulatory element in promoter regions of many cytoprotective genes. Under basal conditions, Nrf2 is constantly targeted for Keap-1-mediated ubiquitination and subsequent proteasomal degradation to maintain low Nrf2 protein levels (25). However, upon activation, Nrf2 can activate downstream antioxidant proteins, phase II metabolizing/detoxifying enzymes and phase III ATP-dependent drug efflux pump-encoded genes (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Effect of ozone oxidative preconditioning on oxidative stress injury in a rat model of kidney transplantation

Qiu

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

The aim of the present study was to investigate the protective effect of ozone oxidative preconditioning (OOP) on renal oxidative stress injury in a rat model of kidney transplantation. Thirty-six male Sprague Dawley (SD) rats were randomly divided into three groups: A sham (S) group, a kidney transplantation (KT) group and an OOP and kidney transplantation (OOP+KT) group. In the S group, the rats' abdomens were opened and closed without transplantation. In the KT group, the rats received a left kidney from donor SD rats. In the OOP+KT group, donor SD rats received 15 OOP treatments by transrectal insufflations (1 mg/kg), once a day, at an ozone concentration of 50 µg/ml, before the kidney transplantation. Twenty-four hours after transplantation, the parameters of renal function of the recipients were measured. The morphology and pathological effects of renal allograft were examined using hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry. Markers of oxidative stress were also detected using the thiobarbituric acid method, and expression levels of Nrf-2 and HO-1 were determined by western blot analysis. Blood urea nitrogen and creatinine levels were significantly decreased in the OOP+KT group compared with the KT group, and the morphology and pathological changes of renal allograft were also less severe. Meanwhile, the renal allograft cell apoptosis index was significantly higher in the KT group compared to the OOP+KT group (P<0.05). Levels of superoxide dismutase, glutathione and catalase in the renal allografts were significantly higher in the OOP+KT group compared to those in the KT group (P<0.05), while malondialdehyde levels were significantly lower in the OOP+KT group compared to those in the KT group (P<0.05). Western blot analysis indicated that the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) were significantly higher in the OOP+KT compared to the KT group (P<0.05). In conclusion, the mechanism by which OOP alleviates oxidative stress injury in renal transplantation may be related to the activation of the signaling pathways of Nrf-2/HO-1 and inhibition of renal tubular epithelial cell apoptosis.

show abstract

“…Coumarin analogues have been reported to activate Nrf2 and related cytoprotective genes (Chang et al, 2015a). Among them, compound 8 (Fig.…”

Section: Synthetic Activatorsmentioning

confidence: 99%

Nrf2 as regulator of innate immunity: A molecular Swiss army knife!

Battino

Giampieri

Pistollato

et al. 2018

Biotechnology Advances

145

View full text Add to dashboard Cite

Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model

Cited by 16 publications

References 44 publications

Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX

Novel 6- and 7-Substituted Coumarins with Inhibitory Action against Lipoxygenase and Tumor-Associated Carbonic Anhydrase IX

Effect of ozone oxidative preconditioning on oxidative stress injury in a rat model of kidney transplantation

Nrf2 as regulator of innate immunity: A molecular Swiss army knife!

Contact Info

Product

Resources

About