1245-15-4Relevant articles and documents
Quercetin 3,7-dimethyl ether: A vasorelaxant flavonoid isolated from Croton schiedeanus Schlecht
Guerrero,Puebla,Carron,Martin,San Roman
, p. 1373 - 1378 (2002)
The vasorelaxant profile of quercetin 3,7-dimethyl ether, a flavonoid isolated from Croton schiedeanus Schlecht (Euphorbiaceae), was assessed in aortic rings isolated from Wistar rats. To gain insight into its structure-activity relationship, we compared this substance with quercetin 3,4′,7-trimethyl ether (ayanin), another flavonoid isolated from this plant, quercetin 3,3′,4′,7-tetramethyl ether, a flavonoid synthesized by us, and quercetin. In addition we examined the interaction of quercetin 3,7-dimethyl ether with the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway. According to their pEC50 values (concentration producing a 50% inhibition of the maximal contractile response) to phenylephrine-induced precontraction in rat isolated aorta, the potency order was quercetin 3,7-dimethyl ether > quercetin > quercetin 3,4′,7-trimethyl ether > quercetin 3,3′,4′,7-tetramethyl ether (4.70 ± 0.18; 3.96 ± 0.07; 3.64 ± 0.02; 3.11 ± 0.16). The relaxant effect of quercetin 3,7-dimethyl ether was significantly decreased by the removal of endothelium as well as by methylene blue, an inhibitor of guanylyl cyclase, and by NG-nitro-L-arginine methyl ester hydrochloride (L-NAME), an NO-synthase inhibitor. Therefore, quercetin 3,7-dimethyl ether has a NO/cGMP pathway-related profile, with increased vasorelaxant activity due to hydroxylation at positions 3 and 4 of the B ring. In addition, methylation at positions 3 and 7 with respect to quercetin of the C and A rings, respectively, seems to further enhance the vasorelaxant activity of quercetin 3,7-dimethyl ether.
Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships
Ko, Wun-Chang,Kuo, Shih-Wu,Sheu, Joen-Rong,Lin, Chien-Huang,Tzeng, Shu-Huey,Chen, Chi-Ming
, p. 273 - 275 (1999)
In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration- dependently relaxed histamine (30 μM), carbachol (0.2 μM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine- induced precontraction, the potency order was quercetin 3,3',4',5,7- pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.
Purification and immunological characterization of a recombinant trimethylflavonol 3'-O-methyltransferase
Seguin, Jacynthe,Muzac, Ingrid,Ibrahim, Ragai K.
, p. 319 - 325 (1998)
A flavonol O-methyltransferase cDNA clone (pF3'OMT) from Chrysosplenium americanum was expressed in Escherichia coli Top 10 and the recombinant protein was purified to near homogeneity by affinity chromatography on chelation resin and gel filtration on Superose 12 columns. The purified protein was enzymatically active as a 42 kDa monomer and exhibited strict specificity for position 3' of 3,7,4'-tri methylquercetin. It did not accept the mono- or dimethyl analogs, the parent aglycone quercetin or the phenylpropanoids, caffeic and 5-hydroxyferulic acids as substrates; thus indicating its involvement in the later steps of polymethylated flavonol synthesis in this plant. The K(m) values of the enzyme for 3,7,4'-tri methylquercetin as substrate and S-adenosyl-L-methionine as co-substrate were 7.2 and 20 μM, respectively. The enzyme activity was strongly inhibited by both Ni2+ and p-chloromercuribenzoate and was restored by the addition of EDTA or β-mercaptoethanol, respectively. Antibodies raised against the F3'OMT recombinant protein recognized a protein band migrating at the expected molecular mass of the enzyme on SDS-poly-acrylamide gels of protein extracts prepared from various sources. This implies a high degree of structural similarity among these enzymes that is also corroborated by their hydropathy profiles.
Synthesis and antiproliferative activities of aminoalkylated polymethoxyflavonoid derivatives
Li, Xue-Li,Zhang, Yan-Hua,Wang, Cai-Fang,Wang, Qiu-An
, p. 1 - 8 (2017)
A series of novel aminoalkylated polymethoxyflavonoid derivatives 3–11 was synthesised from 5-hydroxy-3,7,3′,4′-tetramethoxyflavonoid (1) through extending alkoxy chain at the 5-position, and introducing amine hydrogen bond receptor at the end of the side chain. Their antiproliferative activities were evaluated in vitro on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3). The results showed that all the target compounds exhibited antiproliferative activities against investigated cancer cells with IC50 values of 9.51–53.33?μM. Compounds 5, 7, 8, 11 on Hela cells and compounds 4–9, 11 on HCC1954 exhibited more potency as compared to positive control cis-Platin.
Pentamethylquercetin improves adiponectin expression in differentiated 3t3-l1 cells via a mechanism that implicates pparγ together with tnf-α and il-6
Chen, Lei,He, Ting,Han, Yi,Sheng, Ji-Zhong,Jin, Si,Jin, Man-Wen
, p. 5754 - 5768 (2011)
Adiponectin is an adipocyte-derived hormone that plays a pivotal role in the regulation of lipid and glucose metabolism. Up-regulation of adiponectin expression and production has been shown to benefit for metabolic disorders, including type 2 diabetes, hyperlipidemia, etc. The present study investigated whether the novel polymethoxylated flavonoid pentamethylquercetin (PMQ), a member of polymethoxylated flavonoids family which is present in seabuckthorn (Hippophae L.) would affect adiponectin production in differentiated 3T3-L1 adipocytes. It was found that PMQ increased the adiponectin mRNA and protein expressions in adipocytes in time- and concentration-dependent manners. The PPARγ pathway plays a important roles in this effect of PMQ because blockade of PPARγ by GW9662 eliminates the PMQ-induced up-regulation of adiponectin expression. Furthermore, significant decreases of mRNA expression and secretion of TNF-α and IL-6 were also observed in PMQ-treated cells. Taken together, our study demonstrated that PMQ up-regulates adiponectin expression via a mechanism that implicates PPARγ together with TNF-α and IL-6, suggesting that PMQ might be a potential candidate for the treatment of metabolic diseases.
Synthesis of new 6- and 8-Alkenyl-3,7,3’,4’-Tetramethoxyquercetin derivatives by microwave-assisted Heck coupling
Ramos, Ingrid T. L.,Silva, Tania M. S.,Camara, Celso A.
, p. 2583 - 2589 (2019)
A series of flavonoid derivatives were synthesized from 6- and 8-iodo-3,7,3’4’-tetramethoxy-quercetin with terminal alkenes by microwave-assisted palladium-catalyzed Heck coupling. These alkenes include n-butyl acrylate, 2-methyl-3-buten-2-ol, acrylonitrile, and styrene, providing 10 new substituted flavonoid compounds obtained with moderate to good yields.
Influence of flavonols and quercetin derivative compounds on MA-10 Leydig cells steroidogenic genes expressions
Cormier, Michelle,Ghouili, Firas,Roumaud, Pauline,Martin, Luc J.,Touaibia, Mohamed
, p. 111 - 121 (2017)
Androgen are mainly synthesized and secreted from testicular Leydig cells and play critical roles in testis development, normal masculinization, spermatogenesis, and male fertility. The rate-limiting step in testosterone biosynthesis involves the import of cholesterol inside mitochondria by the steroidogenic acute regulatory (Star) protein. Cholesterol is then converted to pregnenolone by the steroidogenic enzyme Cyp11a1, followed by a chemical transformation to testosterone using other steroidogenic enzymes. Interestingly, levels of Star protein within adult Leydig cells decrease during aging, resulting in defective mitochondrial cholesterol transfer and reduced testosterone production. Such decline may be delayed by increasing Star and/or Cyp11a1 gene expressions using supplementation with flavonoids, a group of the polyphenolic compounds widely distributed in fruits and vegetables. In this study, we examined whether the distribution of hydroxyl groups and/or acetylation or methylation of flavonols could influence their potency to stimulate steroidogenesis within Leydig cells. Low levels of quercetin, myricetin and pentaacetylquercetin (10 μM) stimulated cAMP-dependent Star, Cyp11a1 and Fdx1 promoters' activations and may increase steroidogenesis within Leydig cells. Indeed, pentaacetylquercetin successfully increased cAMP-dependent accumulation of progesterone from MA-10 Leydig cells, possibly through activation of Star and Cyp11a1 transcriptions. Thus, dietary supplementation of pentaacetylquercetin could be potentially effective to maintain testosterone production within aging males.
Methylation of Quercetin by Diazomethane and Hypoglycemic Activity of its Tetra-O-Methyl Ether
Karimova,Baltina,Spirikhin,Sapozhnikova,Gabdrakhmanova,Makara
, p. 837 - 841 (2020)
The tetra-O-methyl ether of quercetin (QU) 3 (54%), 3,7,4′-tri-O-methyl ether 4 (30%), and a previously unreported 3,7,3-tri-O-methyl ether of QU 5 (7%) were obtained via methylation of QU by an excess of diazomethane in dioxane. Their structures were established using 2D NMR (1H–1H COSY, 1H–1H NOESY, 1H–13C HSQC, 1H–13C HMBC). Tetra-O-methyl ether of QU 3 exhibited pronounced hypoglycemic activity, reduced alloxan-induced hyperglycemia in rats by 44.5% compared to a control, and was 2.7 times more active than QU.
Cytotoxic and NF-κB inhibitory sesquiterpene lactones from Piptocoma rufescens
Ren, Yulin,Acu?a, Ulyana Mu?oz,Jiménez, Francisco,García, Ricardo,Mejía, Melciades,Chai, Heebyung,Gallucci, Judith C.,Farnsworth, Norman R.,Soejarto, Djaja D.,Carcache De Blanco, Esperanza J.,Kinghorn, A. Douglas
, p. 2671 - 2678 (2012)
Six new (1-6) and eight known germacranolide-type sesquiterpene lactones, along with several known phenylpropanol coumarates and methylated flavonoids, were isolated from the leaves of Piptocoma rufescens, collected in the Dominican Republic. The new compounds were identified by analysis of their spectroscopic data, with the molecular structure of 3 being established by single-crystal X-ray diffraction. The absolute configurations of the sesquiterpene lactones isolated were determined from their CD and NOESY NMR spectra, together with the analysis of Mosher ester reactions. Bioassay screening results showed the majority of the sesquiterpene lactones isolated (1-13) to be highly cytotoxic toward the HT-29 human colon cancer cell line, with the most potent compound being 15-deoxygoyazensolide (10, IC50, 0.26 μM). In addition, several of the sesquiterpene lactones exhibited NF-κB (p65) inhibitory activity.
Pharmacokinetics and Metabolites of 12 Bioactive Polymethoxyflavones in Rat Plasma
Chen, Hongping,Ding, Haiyan,Hu, Yuan,Li, Dan,Liu, Youping,You, Qiang
, p. 12705 - 12716 (2021/11/17)
Polymethoxyflavones (PMFs) are a subgroup of flavonoids possessing various health benefits. 3,5,7,4′-Tetramethoxyflavone (1), 5,6,7,4′-tetramethylflavone (2), 3,7,3′,4′-tetramethoxyflavone (3), 5,7,3′,4′-tetramethoxyflavone (4), 5-hydroxy-3,7,2′,4′-tetramethoxyflavone (5), 3,5,7,2′,4′-pentamethoxyflavone (6), 5-hydroxy-3,7,3′,4′-tetramethoxyflavone (7), 3-hydroxy-5,7,3′,4′-tetramethylflavone (8), 3,5,7,3′,4′-pentamethoxyflavone (9), 5-hydroxy-3,7,3′,4′,5′-pentamethoxyflavone (10), 3-hydroxy-5,7,3′,4′,5′-pentamethoxyflavone (11), and 3,5,7,3′,4′,5′-hexamethoxylflavone (12) were 12 bioactive and available PMFs. The aim of this study was to investigate the pharmacokinetic, metabolite, and antitumor activities as well as the structure-pharmacokinetic-antitumor activity relationships of these 12 PMFs to facilitate further studies of their medicinal potentials. The cytotoxicity of PMFs with a hydroxy group toward HeLa, A549, HepG2, and HCT116 cancer cell lines was generally significantly more potent than that of PMFs without a hydroxy group. Compounds 5, 7, 8, 10, and 11 were all undetectable in rat plasma, while compounds 1-4, 6, 9, and 12 were detectable. Both the number and position of hydroxy and methoxy groups played an important role in modulating PMF pharmacokinetics and metabolites.
