2. Academic Validation
  3. Design, synthesis and biological evaluation of novel arylpropionic esters for the treatment of acute kidney injury

Design, synthesis and biological evaluation of novel arylpropionic esters for the treatment of acute kidney injury

  • Bioorg Chem. 2020 Dec;105:104455. doi: 10.1016/j.bioorg.2020.104455.
Jiawei Zuo 1,  Shi-Meng Wang 2,  Xia Jiang 3,  Mengxin Cao 3,  Ziwen Zhang 3,  Tianlu Shi 4,  Hua-Li Qin 5,  Wenjian Tang 6
Affiliations

Affiliations

  • 1 School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei 230032, China; First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
  • 2 School of Life Science, Wuchang University of Technology, Wuhan 430223, China; School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China.
  • 3 School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei 230032, China.
  • 4 First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
  • 5 School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan 430070, China. Electronic address: [email protected].
  • 6 School of Pharmacy, Anhui Province Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, Hefei 230032, China. Electronic address: [email protected].
PMID: 33197847 DOI: 10.1016/j.bioorg.2020.104455
Abstract

Acute kidney injury (AKI) is associated with a strong inflammatory response, and inhibiting the response effectively prevents or ameliorates AKI. A series of novel arylpropionic esters were designed, synthesized and evaluated their biological activity in LPS-stimulated RAW264.7 cells. Novel arylpropionic esters bearing multi-functional groups showed significant anti-inflammatory activity, in which, compound 13b exhibited the most potent activity through dose-dependent inhibiting the production of nitric oxide (NO, IC50 = 3.52 μM), TNF-α and IL-6 (84.1% and 33.6%, respectively), as well as suppressing the expression of iNOS, COX-2 and TLR4 proteins. In C57BL/6 mice with cisplatin-induced AKI, compound 13b improved kidney function, inhibited inflammatory development, and reduced pathological damage of kidney tissues. In brief, this arylpropionic ester scaffold may be developed as anti-inflammatory agents.

Keywords

Acute kidney injury; Anti-inflammatory; Arylpropionic acid; Multi-functional group; Quinoline.

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