2. Academic Validation
  3. Design, synthesis, and bioactivity evaluation of novel amide/sulfonamide derivatives as potential anti-inflammatory agents against acute lung injury and ulcerative colitis

Design, synthesis, and bioactivity evaluation of novel amide/sulfonamide derivatives as potential anti-inflammatory agents against acute lung injury and ulcerative colitis

  • Eur J Med Chem. 2023 Nov 5;259:115706. doi: 10.1016/j.ejmech.2023.115706.
Pan Chen 1,  Jun Yang 2,  Ying Zhou 2,  Xiaobo Li 2,  Yu Zou 2,  Zhiwei Zheng 2,  Mi Guo 2,  Zhichao Chen 2,  Won-Jea Cho 3,  Nipon Chattipakorn 4,  Wenqi Wu 5,  Qidong Tang 6,  Guang Liang 7
Affiliations

Affiliations

  • 1 Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China; College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China.
  • 2 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
  • 3 College of Pharmacy, Chonnam National University, Gwangju, 61186, Republic of Korea.
  • 4 Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
  • 5 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China. Electronic address: [email protected].
  • 6 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China. Electronic address: [email protected].
  • 7 Department of Pharmacy and Institute of Inflammation, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, 310014, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001, China. Electronic address: [email protected].
PMID: 37572538 DOI: 10.1016/j.ejmech.2023.115706
Abstract

The uneven regulation of inflammation is related to various diseases, making anti-inflammation a potential option for the development of novel therapies. In this study, we designed and synthesized a total of fifty-eight novel amide/sulfonamide derivatives based on our previously reported anti-inflammatory compounds. The anti-inflammatory activities of these compounds were evaluated upon LPS-stimulated J774A.1 cells. Compounds 11a, 11b, 11c, and 11d potently reduced the release of IL-6 and TNF-α, and decreased the mRNA level of cytokines in J774A.1 cells. The most active compound 11d with IC50 value of 0.61 μM for IL-6 inhibition, and 4.34 μM for TNF-α inhibition restored IκB α and inhibited the translocation of phosphorylated p65 into the nucleus. In vivo evaluation indicated that 11d improved LPS-induced ALI and alleviated DSS-induced ulcerative colitis in mice. In conclusion, these results suggested compound 11d can be a new lead structure for the development of anti-inflammatory drugs against ALI and ulcerative colitis.

Keywords

Acute lung injury; Amide/sulfonamide; Anti-inflammation; NF-κB pathway; Ulcerative colitis.

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