TY - JOUR
T1 - Natural products as IL-6 inhibitors for inflammatory diseases
T2 - Synthetic and SAR perspective
AU - Harmalkar, Dipesh S.
AU - Sivaraman, Aneesh
AU - Nada, Hossam
AU - Lee, Joohan
AU - Kang, Hyeseul
AU - Choi, Yongseok
AU - Lee, Kyeong
N1 - Publisher Copyright:
© 2024 Wiley Periodicals LLC.
PY - 2024/7
Y1 - 2024/7
N2 - Interleukin-6 (IL-6), a pleiotropic cytokine, plays a pivotal role in the pathophysiology of various diseases including diabetes, atherosclerosis, Alzheimer's disease, multiple myeloma, rheumatoid arthritis, and prostate cancer. The signaling pathways associated with IL-6 offer promising targets for therapeutic interventions in inflammatory diseases and IL-6-dependent tumors. Although certain anti-IL-6 monoclonal antibodies are currently employed clinically, their usage is hampered by drawbacks such as high cost and potential immunogenicity, limiting their application. Thus, the imperative arises to develop novel small non-peptide molecules acting as IL-6 inhibitors. Various natural products derived from diverse sources have been investigated for their potential to inhibit IL-6 activity. Nevertheless, these natural products remain inadequately explored in terms of their structure-activity relationships. In response, our review aims to provide syntheses and structure activity perspective of natural IL-6 inhibitors. The comprehensive amalgamation of information presented in this review holds the potential to serve as a foundation for forthcoming research endeavors by medicinal chemists, facilitating the design of innovative IL-6 inhibitors to address the complexities of inflammatory diseases.
AB - Interleukin-6 (IL-6), a pleiotropic cytokine, plays a pivotal role in the pathophysiology of various diseases including diabetes, atherosclerosis, Alzheimer's disease, multiple myeloma, rheumatoid arthritis, and prostate cancer. The signaling pathways associated with IL-6 offer promising targets for therapeutic interventions in inflammatory diseases and IL-6-dependent tumors. Although certain anti-IL-6 monoclonal antibodies are currently employed clinically, their usage is hampered by drawbacks such as high cost and potential immunogenicity, limiting their application. Thus, the imperative arises to develop novel small non-peptide molecules acting as IL-6 inhibitors. Various natural products derived from diverse sources have been investigated for their potential to inhibit IL-6 activity. Nevertheless, these natural products remain inadequately explored in terms of their structure-activity relationships. In response, our review aims to provide syntheses and structure activity perspective of natural IL-6 inhibitors. The comprehensive amalgamation of information presented in this review holds the potential to serve as a foundation for forthcoming research endeavors by medicinal chemists, facilitating the design of innovative IL-6 inhibitors to address the complexities of inflammatory diseases.
KW - IL-6 inhibitors
KW - inflammatory disease
KW - natural products
KW - structure activity relationships
KW - synthesis
UR - http://www.scopus.com/inward/record.url?scp=85184193677&partnerID=8YFLogxK
U2 - 10.1002/med.22022
DO - 10.1002/med.22022
M3 - Review article
C2 - 38305581
AN - SCOPUS:85184193677
SN - 0198-6325
VL - 44
SP - 1683
EP - 1726
JO - Medicinal Research Reviews
JF - Medicinal Research Reviews
IS - 4
ER -