Publication: Quercetin analogs with high fetal hemoglobin-inducing activity
19
Issued Date
2019-10-01
Resource Type
ISSN
15548120
10542523
10542523
Other identifier(s)
2-s2.0-85069908752
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Medicinal Chemistry Research. Vol.28, No.10 (2019), 1755-1765
Suggested Citation
Wachirachai Pabuprapap, Yanisa Wassanatip, Pichit Khetkam, Waraluck Chaichompoo, Sukanya Kunkaewom, Pongpan Senabud, Janejira Hata, Ratchanaporn Chokchaisiri, Saovaros Svasti, Apichart Suksamrarn Quercetin analogs with high fetal hemoglobin-inducing activity. Medicinal Chemistry Research. Vol.28, No.10 (2019), 1755-1765. doi:10.1007/s00044-019-02412-7 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/50553
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Quercetin analogs with high fetal hemoglobin-inducing activity
Other Contributor(s)
Abstract
© 2019, Springer Science+Business Media, LLC, part of Springer Nature. 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 4ʹ-positions and the free hydroxyl group at the 7-position are required for strong HbF-inducing activity.