2. Academic Validation
  3. Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors

Synthesis and biological evaluation of novel 1-(aryl-aldehyde-oxime)uracil derivatives as a new class of thymidine phosphorylase inhibitors

  • Eur J Med Chem. 2018 Jan 20:144:41-51. doi: 10.1016/j.ejmech.2017.12.016.
Shuyue Zhao 1,  Ke Li 2,  Yi Jin 3,  Jun Lin 4
Affiliations

Affiliations

  • 1 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
  • 2 Department of Medical Oncology, The Third Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming 650031, PR China.
  • 3 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: jinyi@ynu.edu.cn.
  • 4 Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China. Electronic address: linjun@ynu.edu.cn.
PMID: 29247859 DOI: 10.1016/j.ejmech.2017.12.016
Abstract

A novel series of 1-(aryl aldehyd oxime) uracil derivatives were synthesized, characterized and evaluated for its inhibitory activity against thymidine Phosphorylase. Among them, the compound 8d, 8e, 8f, 8g and 8l displayed potent thymidine Phosphorylase inhibitory activities with the IC50 values ranging between 0.12 ± 0.05 and 7.2 ± 1.4 μM. And the compounds 8a, 8h, 8i, 8j, 8m, 8n, 8o, 8q, 8s, 8t and 8u (IC50 is from 10.7 to 39.9 μM) showed a good thymidine Phosphorylase inhibition when compared to the standard 7DX and TPI. The most biologically active compound 8l was demonstrated to be a competition mode of enzyme inhibition. The Molecular docking analysis showed the interaction of these newly synthesized compounds at the active binding site of thymidine Phosphorylase based on the experimental results. In general, these results indicated these compounds are promising inhibitors of thymidine Phosphorylase for the potential treatment of anti-angiogenesis.

Keywords

1-(aryl-aldehyde-oxime)-uracil; Activities/thymidine phosphorylase; Derivatives/anti-proliferative; Inhibitory/docking studies.

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