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Synthesis and evaluation of hydroxychalcones as multifunctional non-purine xanthine oxidase inhibitors for the treatment of hyperuricemia.
Bioorg Med Chem Lett. 2017 08 01; 27(15):3602-3606.BM

Abstract

A series of hydroxychalcone derivatives have been designed, synthesized and evaluated for human xanthine oxidase (XO) inhibitory activity. Most of the tested compounds acted moderate XO inhibition with IC50 values in the micromolar rang. Molecular docking and kinetic studies have been performed to explain the binding modes of XO with the selected compounds. In addition, in vitro antioxidant screening results indicated that some of the hydroxychalcones possessed good anti-free radical activities. Furthermore, the preferred compounds 16 and 18 were able to significantly inhibit hepatic xanthine oxidase activity and reduced serum uric acid level of hyperuricemic mice in vivo. In summary, compounds 16 and 18 with balanced activities of antioxidant, XO inhibition and serum uric acid reduction, which are promising candidates for the treatment of hyperuricemia and gout.

Authors+Show Affiliations

First Affiliated Hospital, Guangxi Medical University, Nanning, PR China.First Affiliated Hospital, Guangxi Medical University, Nanning, PR China.First Affiliated Hospital, Guangxi Medical University, Nanning, PR China.First Affiliated Hospital, Guangxi Medical University, Nanning, PR China.First Affiliated Hospital, Guangxi Medical University, Nanning, PR China.First Affiliated Hospital, Guangxi Medical University, Nanning, PR China.Department of Orthopedics, First Affiliated Hospital, Guangxi Medical University, Nanning, PR China. Electronic address: 274021690@qq.com.Department of Orthopedics, First Affiliated Hospital, Guangxi Medical University, Nanning, PR China. Electronic address: liuyun200450250@sina.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28655421

Citation

Xie, Zhaodi, et al. "Synthesis and Evaluation of Hydroxychalcones as Multifunctional Non-purine Xanthine Oxidase Inhibitors for the Treatment of Hyperuricemia." Bioorganic & Medicinal Chemistry Letters, vol. 27, no. 15, 2017, pp. 3602-3606.
Xie Z, Luo X, Zou Z, et al. Synthesis and evaluation of hydroxychalcones as multifunctional non-purine xanthine oxidase inhibitors for the treatment of hyperuricemia. Bioorg Med Chem Lett. 2017;27(15):3602-3606.
Xie, Z., Luo, X., Zou, Z., Zhang, X., Huang, F., Li, R., Liao, S., & Liu, Y. (2017). Synthesis and evaluation of hydroxychalcones as multifunctional non-purine xanthine oxidase inhibitors for the treatment of hyperuricemia. Bioorganic & Medicinal Chemistry Letters, 27(15), 3602-3606. https://doi.org/10.1016/j.bmcl.2017.01.053
Xie Z, et al. Synthesis and Evaluation of Hydroxychalcones as Multifunctional Non-purine Xanthine Oxidase Inhibitors for the Treatment of Hyperuricemia. Bioorg Med Chem Lett. 2017 08 1;27(15):3602-3606. PubMed PMID: 28655421.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and evaluation of hydroxychalcones as multifunctional non-purine xanthine oxidase inhibitors for the treatment of hyperuricemia. AU - Xie,Zhaodi, AU - Luo,Xiaoting, AU - Zou,Zhuan, AU - Zhang,Xiao, AU - Huang,Feifei, AU - Li,Ruishan, AU - Liao,Shijie, AU - Liu,Yun, Y1 - 2017/01/19/ PY - 2016/10/19/received PY - 2017/01/15/revised PY - 2017/01/17/accepted PY - 2017/6/29/pubmed PY - 2017/8/19/medline PY - 2017/6/29/entrez KW - Antioxidant KW - Hydroxychalcone derivatives KW - Hyperuricemia KW - Xanthine oxidase SP - 3602 EP - 3606 JF - Bioorganic & medicinal chemistry letters JO - Bioorg. Med. Chem. Lett. VL - 27 IS - 15 N2 - A series of hydroxychalcone derivatives have been designed, synthesized and evaluated for human xanthine oxidase (XO) inhibitory activity. Most of the tested compounds acted moderate XO inhibition with IC50 values in the micromolar rang. Molecular docking and kinetic studies have been performed to explain the binding modes of XO with the selected compounds. In addition, in vitro antioxidant screening results indicated that some of the hydroxychalcones possessed good anti-free radical activities. Furthermore, the preferred compounds 16 and 18 were able to significantly inhibit hepatic xanthine oxidase activity and reduced serum uric acid level of hyperuricemic mice in vivo. In summary, compounds 16 and 18 with balanced activities of antioxidant, XO inhibition and serum uric acid reduction, which are promising candidates for the treatment of hyperuricemia and gout. SN - 1464-3405 UR - https://www.unboundmedicine.com/medline/citation/28655421/Synthesis_and_evaluation_of_hydroxychalcones_as_multifunctional_non_purine_xanthine_oxidase_inhibitors_for_the_treatment_of_hyperuricemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-894X(17)30067-7 DB - PRIME DP - Unbound Medicine ER -