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Compounds containing trace element copper or zinc exhibit as potent hyperuricemia inhibitors via xanthine oxidase inactivation.
J Trace Elem Med Biol. 2018 Sep; 49:72-78.JT

Abstract

Compounds containing trace elements copper or zinc are potential gout and hyperuricemia suppressant by virtue of their inhibiting effect on xanthine oxidase/xanthine dehydrogenase (XOD/XDH) and anti-inflammatory and anti-oxidative function. In this study, compounds Cu(hmy-paa)·SO4·H2O (simplified as CuHP) and Zn(hmy-paa)·SO4·H2O (simplified as ZnHP) are synthesized, where hmy-paa stands for 3-(4-hydroxy-3-methoxyphenyl)-N-(1H-pyrazol-3-yl)acrylamide). The ligand hmy-paa is composed of functional ferulic acid and 3-aminopyrazole. The XOD and XDH activity of the mouse liver homogenate could efficiently be inhibited by CuHP and ZnHP. XOD has been recognized as one of the promising targets for the treatment of hyperuricemia. Fluorescence spectrometry study indicates that the interaction between the compound and XOD could be strengthened by the introduction of metals. In vitro drug efficacy study illustrates that metals copper and zinc distinctly improves the uric acid reducing efficacy by suppressing XOD activation. Hyperuricemia mouse model is induced by co-treatment of hypoxanthine and oteracil potassium. Intraperitoneal injection of CuHP and ZnHP to hyperuricemia mice exhibits a significant effect on reducing serum uric acid. The serum creatinine value detection indicates that the side effect of CuHP and ZnHP on renal function is weak. The computational docking simulation exhibits the tightly binding mode between the compound and XOD. Consequently, compounds CuHP and ZnHP are new type candidates for the treatment of gout and hyperuricemia.

Authors+Show Affiliations

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 211198, Jiangsu, PR China. Electronic address: wenzhou@cpu.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29895374

Citation

Li, Lan-Zhu, et al. "Compounds Containing Trace Element Copper or Zinc Exhibit as Potent Hyperuricemia Inhibitors Via Xanthine Oxidase Inactivation." Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS), vol. 49, 2018, pp. 72-78.
Li LZ, Zhou GX, Li J, et al. Compounds containing trace element copper or zinc exhibit as potent hyperuricemia inhibitors via xanthine oxidase inactivation. J Trace Elem Med Biol. 2018;49:72-78.
Li, L. Z., Zhou, G. X., Li, J., Jiang, W., Liu, B. L., & Zhou, W. (2018). Compounds containing trace element copper or zinc exhibit as potent hyperuricemia inhibitors via xanthine oxidase inactivation. Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS), 49, 72-78. https://doi.org/10.1016/j.jtemb.2018.04.019
Li LZ, et al. Compounds Containing Trace Element Copper or Zinc Exhibit as Potent Hyperuricemia Inhibitors Via Xanthine Oxidase Inactivation. J Trace Elem Med Biol. 2018;49:72-78. PubMed PMID: 29895374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Compounds containing trace element copper or zinc exhibit as potent hyperuricemia inhibitors via xanthine oxidase inactivation. AU - Li,Lan-Zhu, AU - Zhou,Guo-Xiu, AU - Li,Jia, AU - Jiang,Wei, AU - Liu,Bao-Lin, AU - Zhou,Wen, Y1 - 2018/04/22/ PY - 2018/01/22/received PY - 2018/03/20/revised PY - 2018/04/18/accepted PY - 2018/6/14/entrez PY - 2018/6/14/pubmed PY - 2018/10/10/medline KW - Copper & zinc KW - Ferulic acid KW - Hyperuricemia KW - XOD/XDH inhibitor SP - 72 EP - 78 JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) JO - J Trace Elem Med Biol VL - 49 N2 - Compounds containing trace elements copper or zinc are potential gout and hyperuricemia suppressant by virtue of their inhibiting effect on xanthine oxidase/xanthine dehydrogenase (XOD/XDH) and anti-inflammatory and anti-oxidative function. In this study, compounds Cu(hmy-paa)·SO4·H2O (simplified as CuHP) and Zn(hmy-paa)·SO4·H2O (simplified as ZnHP) are synthesized, where hmy-paa stands for 3-(4-hydroxy-3-methoxyphenyl)-N-(1H-pyrazol-3-yl)acrylamide). The ligand hmy-paa is composed of functional ferulic acid and 3-aminopyrazole. The XOD and XDH activity of the mouse liver homogenate could efficiently be inhibited by CuHP and ZnHP. XOD has been recognized as one of the promising targets for the treatment of hyperuricemia. Fluorescence spectrometry study indicates that the interaction between the compound and XOD could be strengthened by the introduction of metals. In vitro drug efficacy study illustrates that metals copper and zinc distinctly improves the uric acid reducing efficacy by suppressing XOD activation. Hyperuricemia mouse model is induced by co-treatment of hypoxanthine and oteracil potassium. Intraperitoneal injection of CuHP and ZnHP to hyperuricemia mice exhibits a significant effect on reducing serum uric acid. The serum creatinine value detection indicates that the side effect of CuHP and ZnHP on renal function is weak. The computational docking simulation exhibits the tightly binding mode between the compound and XOD. Consequently, compounds CuHP and ZnHP are new type candidates for the treatment of gout and hyperuricemia. SN - 1878-3252 UR - https://www.unboundmedicine.com/medline/citation/29895374/Compounds_containing_trace_element_copper_or_zinc_exhibit_as_potent_hyperuricemia_inhibitors_via_xanthine_oxidase_inactivation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0946-672X(18)30084-1 DB - PRIME DP - Unbound Medicine ER -