131359-24-5 Usage
Description
Nrf2 activation of the antioxidant response element (ARE) is central to cytoprotective gene expression against oxidative and/or electrophilic stress. Unless activated by inflammatory, environmental, or oxidative stressors, Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. Because of its protective capabilities, small molecules that activate Nrf2 signaling are being examined as potential anti-cancer or anti-inflammatory agents. 2-HBA, a synthetic analog of curcumin, is an indirect inducer of enzymes that catalyze detoxification reactions through the Keap1-Nrf2-ARE pathway. As a double Michael reaction acceptor, 2-HBA can directly modify cysteine sulfhydryl groups in Keap1 and consequently suppress Nrf2 ubiquitination, which leads to enhanced expression of antioxidative and cytoprotective enzymes. 2-HBA doubles the specific activity of NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1) in Hepa1c1c7 cells at 0.15 μM. In rapidly dividing mouse leukemia L1210 cells, 0.6 μM 2-HBA increases the activities of NQO1, glutathione reductase, and the levels of total glutathione. At 5-15 μM, 2-HBA causes G2/M cell cycle arrest and p53-independent, caspase 3-mediated apoptosis.
Uses
(E,E)-Bis(2-hydroxybenzylidene)acetone (2-HBA) is a synthetic analogue of curcumin that displays strong NAD(P)H:quinone reductase (NQO1) inducer potency in Hepa 1c1c7 cells. 2-HBA, a double Michael reaction acceptor, can directly modify cysteine sulfhydryl groups in Keap1 and consequently suppress Nrf2 ubiquitination which in turn enhances the expression of antioxidative and cytoprotective enzymes. 2-HBA has also been shown to cause G2/M cell cycle arrest and p53-independent, caspase 3-mediated apoptosis.
in vitro
2-hba could markedly increase the activities of nad(p)h:quinone acceptor oxidoreductase 1 (nqo1) and glutathione reductase, the levels of total glutathione, as well as the phase 2 response markers. in addition, at high concentrations 2-hba caused g2/m cell cycle arrest and apoptosis. moreover, the mutant l1210 cell line was found to be more sensitive to the apoptotic effects of 2-hba [1].
in vivo
the effect of 2-hba on the dmba-induced expression of the ha-ras gene in isolated rna tissues of cba/ca inbred mice was investigated. according to the previous findings, elevated ha-ras expression was obserrved even 24 h after dmba treatment. administration of 2-hba with dmba could lead to a decrease of the dmba-induced ha-ras gene expression in all the investigated tissues, suggesting metabolic interaction of 2-hba and dmba. in addiiton, administration of 2-hba 24 h prior to the dmba treatment was able to reduce the ha-ras gene expression in all tested tissues except the liver, which could be the result of a possible cyp1a inducer and pro-oxidant effects of 2-hba [2].
references
[1] a. t. dinkova-kostova, a. h. cory, r. e. bozak, et al. bis(2-hydroxybenzylidene)acetone, a potent inducer of the phase 2 response, causes apoptosis in mouse leukemia cells through a p53-independent, caspase-mediated pathway. cancer letters 245, 341-349 (2007).[2] perjési p, ember i, bozak re, nádasi e, rozmer z, varjas t, hicks rj. effect of the chalcone analog e,e-bis(2-hydroxybenzylidene) acetone on the 7,12-dimethylbenz[a]anthracene-induced ha-ras gene activity in vivo. in vivo. 2006 jan-feb;20(1):141-6.
Check Digit Verification of cas no
The CAS Registry Mumber 131359-24-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,3,1,3,5 and 9 respectively; the second part has 2 digits, 2 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 131359-24:
(8*1)+(7*3)+(6*1)+(5*3)+(4*5)+(3*9)+(2*2)+(1*4)=105
105 % 10 = 5
So 131359-24-5 is a valid CAS Registry Number.
131359-24-5Relevant articles and documents
Anti-inflammatory activity of ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives in vitro and in vivo
Wang, Ziqing,Mu, Wenwen,Li, Pengxiao,Liu, Guoyun,Yang, Jie
, (2021/02/21)
Curcumin was reported as an anti-inflammatory agent. However, curcumin's poor bioavailability limited its clinical utility. Here, thirty ortho-substituted mono-carbonyl curcumin derivatives, containing acetone, cyclopentanone, cyclohexanone or 4-piperidione (N—H, N-methyl or N-acrylyl) moieties replacing β-diketone moiety of curcumin, were investigated for anti-inflammatory activity. Two active ortho-trifluoromethoxy-substituted 4-piperidione-containing derivatives 22 and 24 owned good cell uptake ability, and displayed excellent anti-inflammatory activity in both lipopolysaccharide-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. They inhibited the production of nitric oxide, reactive oxygen species, malonic dialdehyde and cyclooxygenase-2; and the expression of pro-inflammatory cytokines interleukin-1β, tumor necrosis factor-α and myeloperoxidase; the phosphorylation of mitogen-activated protein kinases; and the nucleus translocation of p65. What's more, 22 or 24 oral administered reduced the severity of clinical symptoms of ulcerative colitis (body weight and disease activity index), and reduced obviously DSS-induced colonic pathological damage (the colon length and histopathology analysis). These results suggested that ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives 22 and 24 were potential anti-inflammatory agents; and offered the important information for design and discovery of more potent anti-inflammatory drug candidates.
Di(ortho-hydroxybenzylidene)acetone as a new acid-base indicator and a chromogenic receptor for anions and guanidine
Goswami, Shyamaprosad,Chakrabarty, Rinku
experimental part, p. 547 - 557 (2012/03/26)
The development of a new simple acid-base indicator di(o- hydroxybenzylidene)acetone (1) is reported as a possible alternative to phenolphthalein and its performance has been compared with those of o-hydroxybenzylideneacetone (2) and p-hydroxybenzylideneacetone (3), two synthetic compounds, and curcumin (4), a natural product occurring in turmeric. Among the four compounds, 1 is found to be the best. It may also be used in the titration of guanidine in non-aqueous solvents (e.g. in dry alcohol). It is also shown to be a chemosensor for anions.
Synthesis and biological evaluation of curcumin-like diarylpentanoid analogues for anti-inflammatory, antioxidant and anti-tyrosinase activities
Lee, Ka-Heng,Ab. Aziz, Farida Haryani,Syahida, Ahmad,Abas, Faridah,Shaari, Khozirah,Israf, Daud Ahmad,Lajis, Nordin Haji
experimental part, p. 3195 - 3200 (2009/12/04)
A series of 46 curcumin related diarylpentanoid analogues were synthesized and evaluated for their anti-inflammatory, antioxidant and anti-tyrosinase activities. Among these compounds 2, 13 and 33 exhibited potent NO inhibitory effect on IFN-γ/LPS-activated RAW 264.7 cells as compared to l-NAME and curcumin. However, these series of diarylpentanoid analogues were not significantly inhibiting NO scavenging, total radical scavenging and tyrosinase enzyme activities. The results revealed that the biological activity of these diarylpentanoid analogues is most likely due to their action mainly upon inflammatory mediator, inducible nitric oxide synthase (iNOS). The present results showed that compounds 2, 13 and 33 might serve as a useful starting point for the design of improved anti-inflammatory agents.
