Antiglycation, radical scavenging, and semicarbazide-sensitive amine oxidase inhibitory activities of acetohydroxamic acid in vitro

Yuh Hwa Liu, Yeh Lin Lu, Der Zen Liu, Wen Chi Hou

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2 Citations (Scopus)

Abstract

Advanced glycation endproducts (AGEs) can promote intracellular reactive oxygen species production, and the levels of AGEs are highly correlated with cardiovascular disease and diabetes complications. Acetohydroxamic acid (acetH) is a bacterial urease inhibitor drug used to treat kidney stones and infections in the urinary tract, and hydroxyurea (HU) is a drug used for antineoplasm and sickle cell diseases. Both acetH and HU are hydroxamic acid derivatives. It was found that acetH and HU at 2.5 or 5 mM showed anti-AGE formation by lowering the AGEs’ fluorescent intensities and Nε-(carboxymethyl)lysine formation in bovine serum albumin/galactose models, and both showed better and significant differences (P<0.05) compared to the positive control of aminoguanidine. Regarding radical scavenging activities, the half-inhibition concentrations (IC50) of acetH against α,α-diphenyl-β-picrylhydrazyl radical and hydroxyl radical were 34.86 and 104.42 µM, respectively. The IC50 of acetH against semicarbazide-sensitive amine oxidase was 10.56 µM, and acetH showed noncompetitive inhibition respective to the substrates (benzylamine). The antiglycation, antioxidant, and semicarbazide-sensitive amine oxidase inhibitory activities of acetH prove that it has the potential for treating cardiovascular disease and diabetes complications and it needs further investigation in animal models.

Original languageEnglish
Pages (from-to)2139-2147
Number of pages9
JournalDrug Design, Development and Therapy
Volume11
DOIs
Publication statusPublished - Jul 13 2017

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Amine Oxidase (Copper-Containing)
Hydroxyurea
Diabetes Complications
Inhibitory Concentration 50
Cardiovascular Diseases
Hydroxamic Acids
Kidney Calculi
Urease
Sickle Cell Anemia
Bovine Serum Albumin
acetohydroxamic acid
In Vitro Techniques
Galactose
Urinary Tract Infections
Pharmaceutical Preparations
Hydroxyl Radical
Reactive Oxygen Species
Animal Models
Antioxidants

Keywords

  • acetH
  • AGEs
  • N-(carboxymethyl)lysine
  • Semicarbazide-sensitive amine oxidase
  • SSAO

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery

Cite this

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title = "Antiglycation, radical scavenging, and semicarbazide-sensitive amine oxidase inhibitory activities of acetohydroxamic acid in vitro",
abstract = "Advanced glycation endproducts (AGEs) can promote intracellular reactive oxygen species production, and the levels of AGEs are highly correlated with cardiovascular disease and diabetes complications. Acetohydroxamic acid (acetH) is a bacterial urease inhibitor drug used to treat kidney stones and infections in the urinary tract, and hydroxyurea (HU) is a drug used for antineoplasm and sickle cell diseases. Both acetH and HU are hydroxamic acid derivatives. It was found that acetH and HU at 2.5 or 5 mM showed anti-AGE formation by lowering the AGEs’ fluorescent intensities and Nε-(carboxymethyl)lysine formation in bovine serum albumin/galactose models, and both showed better and significant differences (P<0.05) compared to the positive control of aminoguanidine. Regarding radical scavenging activities, the half-inhibition concentrations (IC50) of acetH against α,α-diphenyl-β-picrylhydrazyl radical and hydroxyl radical were 34.86 and 104.42 µM, respectively. The IC50 of acetH against semicarbazide-sensitive amine oxidase was 10.56 µM, and acetH showed noncompetitive inhibition respective to the substrates (benzylamine). The antiglycation, antioxidant, and semicarbazide-sensitive amine oxidase inhibitory activities of acetH prove that it has the potential for treating cardiovascular disease and diabetes complications and it needs further investigation in animal models.",
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AU - Liu, Der Zen

AU - Hou, Wen Chi

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