33429-83-3Relevant academic research and scientific papers
Quercetin analogs with high fetal hemoglobin-inducing activity
Pabuprapap, Wachirachai,Wassanatip, Yanisa,Khetkam, Pichit,Chaichompoo, Waraluck,Kunkaewom, Sukanya,Senabud, Pongpan,Hata, Janejira,Chokchaisiri, Ratchanaporn,Svasti, Saovaros,Suksamrarn, Apichart
, p. 1755 - 1765 (2019/08/02)
β-Thalassemia is the major health problems in developing countries, when affected patients and healthy carriers are numerous, resulting a total absence or severe decrease in the production of β-globin chains. The use of chemical agents for increasing the production of fetal hemoglobin (HbF) by reactivating γ-globin gene to balance excess α-globin chains is an alternative therapeutic approach. Therefore, the search for molecules exhibiting the property of inducing γ-globin gene expression is of great interest. In this report, we discovered that quercetin (1), the major flavonoid isolated from the heartwoods of the medicinal plant Anaxagorea luzonensis promoted the expression of γ-globin gene. Chemical modification of 1 to fourteen methyl ether analogs (2?15) was conducted. The structures of these compounds were established on the basis of their spectroscopic data and by comparison with those of the reported values. The parent flavonoid and its chemically modified analogs were investigated for their γ-globin gene induction for the first time. The parent compound 1 exhibited less induced γ-globin gene expression than cisplatin and hemin, the positive controls. 3,4′-Di-O-methylquercetin (7), the modified analog, significantly enhanced γ-globin gene expression with 2.6-fold change at 8 μM, which was slightly higher than cisplatin and hemin. Moreover, compounds 1 and 7 displayed less cytotoxic activity against K562::ΔGγAγEGFP cells than cisplatin. Structure-activity relationship (SAR) study revealed that the methoxyl groups at the 3- and 4?-positions and the free hydroxyl group at the 7-position are required for strong HbF-inducing activity.
Synthesized quercetin derivatives stimulate melanogenesis in B16 melanoma cells by influencing the expression of melanin biosynthesis proteins MITF and p38 MAPK
Yamauchi, Kosei,Mitsunaga, Tohru,Inagaki, Mizuho,Suzuki, Tohru
, p. 3331 - 3340 (2014/06/23)
In order to understand the effect of structure-activity relationships on melanogenesis using B16 melanoma cells, 19 quercetin derivatives were synthesized. Among the synthesized compounds, 3-O-methylquercetin (11) and 3′,4′,7-O-trimethylquercetin (14) increased melanin content more potently than the positive control theophylline, while exhibiting low cytotoxicity. Compound 11 exhibited less melanogenesis-stimulating activity than compound 14. However, 11 increased the expression of tyrosinase and tyrosinase-related protein 1 (TRP-1) to a greater extent than 14, thereby suggesting that melanogenesis in melanoma cells does not depend solely on the expression of the enzymes catalyzing melanin biosynthesis. Furthermore, 14 also stimulated the expression of the microphthalmia-associated transcription factor (MITF) and p-p38 mitogen activated protein kinase (MAPK), while they were not increased by 11. These results suggest that 11 may enhance the expression of tyrosinase and TRP-1 by regulating the proteasomal degradation of melanogenic enzymes and/or by activating other transcriptional factors regulating enzyme expression.
Hemisynthesis of all the O-monomethylated analogues of quercetin including the major metabolites, through selective protection of phenolic functions
Bouktaib, Mohamed,Lebrun, Stéphane,Atmani, Aziz,Rolando, Christian
, p. 10001 - 10009 (2007/10/03)
A new methodology for the hemisynthesis of all the five O-monomethylated analogues of quercetin (3′-O-methylquercetin (isorhamnetin), 4′-O-methylquercetin (tamarixetin), 3-O-methylquercetin, 5-O-methylquercetin (azaleatin) and 7-O-methylquercetin (rhamnetin)) through sequential protection of the different phenolic functions of quercetin is reported.
