Synthesis of a library of glycosylated flavonols

Li, Zhitao; Ngojeh, George; Dewitt, Paul F.; Zheng, Zhi; Chen, Min; Lainhart, Brendan C.; Li, Vincent; Felpo, Peter

doi:10.1016/j.tetlet.2008.10.032

Cited by 28 publications

(16 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the synthesis of α-naphthoflavone derivatives (4a-4o, Scheme 1), compound 1 served as the starting point which was easily prepared from 1,5-dihydroxynaphthalene according to our reported procedure 23 The most commonly used method for the synthesis of flavonols was the Algar-Flynn-Oyamada (AFO) reaction that employed corresponding chalcones as the starting material [24][25][26][27] . However, in the synthesis of 6,7,10-trimethoxy-α-naphthoflavonols (8a-8g), this oxidative cyclization strategy using 2'-hydroxyl benzochalcones (9a-9g, Figure 3) failed to give any desired naphthoflavonols.…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

et al. 2015

View full text Add to dashboard Cite

CYP1B1 is recognized as a new target in cancer prevention and therapy. Taking α-naphthoflavone as a lead, a series of 6,7,10-trimethoxy-α-naphthoflavones (4a-o) were synthesized and evaluated for their inhibitory potency against CYP1B1 and selectivity over CYP1A1 and 1A2. SAR analysis indicated that introducing methoxy groups at C(6), C(7), and C(10) on the naphthalene part and a fluoro atom at C(3') on the B-ring, could sharply increase the efficiency toward CYP1B1 inhibition. Among the prepared derivatives, compound 4c is the most potent and selective CYP1B1 inhibitor ever reported. More effort was taken to acquire water-soluble α-naphthoflavone derivatives for further cell-based study of overcoming anticancer drug-resistance. Finally, we obtained water-soluble naphthoflavone (11f) which could obviously eliminate the docetaxel-resistance caused by the enhanced expression of CYP1B1 in MCF-7/1B1 cells. It could be envisaged that the discovery of new α-naphthoflavones as CYP1B1 inhibitors is clinically important for overcoming CYP1B1-mediated drug-resistance in cancer therapeutics.

show abstract

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

et al. 2015

View full text Add to dashboard Cite

show abstract

“…From a survey of the literature, we found that flavonol derivatives can be achieved by the epoxidation of corresponding flavone compounds or by the Baker–Venkataraman type of sequential cyclization‐dehydration reaction . Another Algar–Flynn–Oyamada reaction has also been widely used to make flavonols . We chose this reaction for the transformation of 3‐methylfuranochalcones 11 to angular 3‐methylfuranoflavonols 12 in the presence of NaOH (2 equiv) and H 2 O 2 (2.2 equiv).…”

Section: Resultsmentioning

confidence: 99%

Diversity-Oriented Synthesis of Natural-Product-like Libraries Containing a 3-Methylbenzofuran Moiety for the Discovery of New Chemical Elicitors

Chen

Lin

et al. 2016

ChemistryOpen

View full text Add to dashboard Cite

Natural products are a major source of biological molecules. The 3‐methylfuran scaffold is found in a variety of plant secondary metabolite chemical elicitors that confer host‐plant resistance against insect pests. Herein, the diversity‐oriented synthesis of a natural‐product‐like library is reported, in which the 3‐methylfuran core is fused in an angular attachment to six common natural product scaffolds—coumarin, chalcone, flavone, flavonol, isoflavone and isoquinolinone. The structural diversity of this library is assessed computationally using cheminformatic analysis. Phenotypic high‐throughput screening of β‐glucuronidase activity uncovers several hits. Further in vivo screening confirms that these hits can induce resistance in rice to nymphs of the brown planthopper Nilaparvata lugens. This work validates the combination of diversity‐oriented synthesis and high‐throughput screening of β‐glucuronidase activity as a strategy for discovering new chemical elicitors.

show abstract

“…The Claisen-Schmidt condensation of substituted benzaldehyde (3) and acetophenone derivative (1) (Goel and Dixit, 2004) in presence of aqueous potassium hydroxide produced corresponding chalcone (4) . Resulted chalcone was converted to benzylated furanoflavonoid (5) using Algar-Flynn-Oyamada reaction (Zhitao et al, 2008) by treatment with alkaline hydrogen peroxide. Further, it was debenzylated using TiCl 4 (Selvam et al, 2009) in dry DCM under N 2 atmosphere affording 3,3 0 ,4 0 -trihydroxy-4H-furo[2,3-h]chromen-4-one (6) (Scheme 1; Fig.…”

Section: Chemistrymentioning

confidence: 99%

“…R 1 = R 2 = R 4 = H, R 3 = OCH 2 Ph (f). R 1 = R 4 = H, R 2 = OMe, R 3 = OCH 2 Ph (g on type 2 diabetes mellitus has advocated that a-glucosidase inhibitors are most effective in reducing PPHG in typical Asian dietary conditions (Zhitao et al, 2008). Its use is also associated with a slight decrease in fasting glucose concentrations.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of antihyperglycemic, α-glucosidase inhibitory, and DPPH free radical scavenging furanochalcones

et al. 2011

View full text Add to dashboard Cite

A series of furanochalcone derivatives have been designed and synthesized. Molecular modeling studies were carried out to probe into the mechanism of binding of chalcone inhibitors and understand the structure-activity relationship to identify the contribution of scaffolds and groups in the synthesized analogs to biological activity. The three-dimensional model of a-glucosidase was constructed based on the crystal structure family 31 a-glycosidase (PDB 1XSI) using Modeller9v5. Docking of the inhibitors on the built homology model revealed interactions in the active site region mostly with Asp 252, Tyr254, Gln523, and Arg571. 2D-QSAR models were generated with CODESSA using Heuristic method. The best predictive model was generated using three descriptors that gave a correlation co-efficient (r 2 ) 0.9886 and cross-validate (r 2 ) 0.9338. The synthesized compounds were screened against the a-glucosidase inhibition and DPPH radical scavenging properties. All the synthetic compounds displayed varying degrees of a-glucosidase inhibitory and DPPH scavenging activities. Compound 8c was found most potent a-glucosidase inhibitor though; it could not display DPPH scavenging activity. When tested in vivo for antihyperglycemic activity in starch-loaded Wistar rats, 8c was equally effective in reducing time-dependent hyperglycemia as to the standard drug, Acarbose. Compound 8c may serve as an interesting compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes.

show abstract

Synthesis of a library of glycosylated flavonols

Cited by 28 publications

References 24 publications

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

Design and Synthesis of New α-Naphthoflavones as Cytochrome P450 (CYP) 1B1 Inhibitors To Overcome Docetaxel-Resistance Associated with CYP1B1 Overexpression

Diversity-Oriented Synthesis of Natural-Product-like Libraries Containing a 3-Methylbenzofuran Moiety for the Discovery of New Chemical Elicitors

Synthesis of antihyperglycemic, α-glucosidase inhibitory, and DPPH free radical scavenging furanochalcones

Contact Info

Product

Resources

About