One-pot synthesis of thioxo-tetrahydropyrimidine derivatives as potent β-glucuronidase inhibitor, biological evaluation, molecular docking and molecular dynamics studies
高效β-葡萄糖醛酸酶抑制剂硫代四氢嘧啶衍生物的一锅法合成、生物学评价、分子对接和分子动力学研究
作者: Aida IrajiAli NouriNajmeh EdrakiSomayeh PirhadiMahsima KhoshneviszadehMehdi Khoshneviszadeh
作者单位: 1Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
刊名: Bioorganic & Medicinal Chemistry, 2020, Vol.28 (7)
来源数据库: Elsevier Journal
DOI: 10.1016/j.bmc.2020.115359
关键词: Β-glucuronidaseThioxo-tetrahydropyrimidineSynthesisDockingMolecular dynamics
英文摘要: Abstract(#br)A series of N,N -diethyl phenyl thioxo-tetrahydropyrimidine carboxamide have been synthesized and investigated for their β-glucuronidase inhibitory activities. All molecules exhibited excellent inhibition with IC 50 values ranging from 0.35 to 42.05 µM and found to be even more potent than the standard d -saccharic acid. Structure-activity relationship analysis indicated that the meta -aryl-substituted derivatives significantly influenced β-glucuronidase inhibitory activities while the para -substitution counterpart outperforming moderate potency. The most potent compound in this series was 4g bearing thiophene motif with IC 50 of 0.35 ± 0.09 µM. To verify the SAR, molecular docking and molecular dynamics studies were also performed.
全文获取路径: Elsevier  (合作)
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影响因子:2.903 (2012)

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关键词翻译
关键词翻译
  • glucuronidase 葡糖苷酸酶
  • dynamics 动力学
  • synthesis 合成
  • docking 靠泊
  • molecular 分子的
  • biological 生物学的
  • potent 强大的
  • inhibitor 抑制剂
  • derivatives 派生物
  • evaluation 评价