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Synthesis of benzoxazole derivatives as interleukin-6 antagonists

Title
Synthesis of benzoxazole derivatives as interleukin-6 antagonists
Authors
Kim D.Won H.Y.Hwang E.S.Kim Y.-K.Choo H.-Y.P.
Ewha Authors
박혜영황은숙
SCOPUS Author ID
박혜영scopus; 황은숙scopus
Issue Date
2017
Journal Title
Bioorganic and Medicinal Chemistry
ISSN
0968-0896JCR Link
Citation
vol. 25, no. 12, pp. 3127 - 3134
Keywords
Benzoxazole derivativesIFN-γIL-17IL-4IL-6-STAT3
Publisher
Elsevier Ltd
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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. © 2017
DOI
10.1016/j.bmc.2017.03.072
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약학대학 > 약학과 > Journal papers
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