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
  • 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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