Synthesis of benzoxazole derivatives as interleukin-6 antagonists

Darong Kim, Hee Yeon Won, Eun Sook Hwang, Young Kook Kim, Hea Young Park Choo

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


A growing number of studies have demonstrated that interleukin (IL)-6 plays pathological roles in the development of chronic inflammatory disease and autoimmune disease by activating innate immune cells and by stimulating adaptive inflammatory T cells. So, suppression of IL-6 function may be beneficial for prevention and treatment of chronic inflammatory disease. This study reports that a series of synthetic derivatives of benzoxazole have suppressive effects on IL-6-mediated signaling. Among 16 synthetic derivatives of benzoxazole, the compounds 4, 6, 11, 15, 17, and 19 showed a strong suppressive activity against IL-6-induced phosphorylation of signal transducer and activator of transcription (STAT) 3 by 80–90%. While the cell viability was strongly decreased by compounds 11, 17, 19, the compounds 4, 6, and 15 revealed less cytotoxicity. We then examined the effects of the compounds on inflammatory cytokine production by CD4+ T cells. CD4+ T cells were induced to differentiate into interferon (IFN)-γ-, IL-17-, or IL-4-producing effector T cells in the presence of either the compound 4 or the compound 7. While the inactive compound 7 had no significant effect on the cytokine production by effector T cells, the active compound 4 strongly suppressed the production of inflammatory cytokines IFN-γ and IL-17, and also inhibited allergic inflammatory cytokines IL-4, IL-5, and IL-13 produced by effector Th2 cells. These results suggest that a benzoxazole derivative, compound 4 effectively suppresses IL-6-STAT3 signaling and inflammatory cytokine production by T cells and provides a beneficial effect for treating chronic inflammatory and autoimmune disease.

Original languageEnglish
Pages (from-to)3127-3134
Number of pages8
JournalBioorganic and Medicinal Chemistry
Issue number12
StatePublished - 2017

Bibliographical note

Funding Information:
This work was supported by Mid-career Researcher Program through National Research Foundation (NRF) grant funded by the Korean Government (for ESH, NRF-2013R1A2A2A01068302).

Publisher Copyright:
© 2017


  • Benzoxazole derivatives
  • IFN-γ
  • IL-17
  • IL-4
  • IL-6-STAT3


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