TY - JOUR
T1 - Exploring the Anti-inflammatory Potential of Novel Chrysin Derivatives through Cyclooxygenase-2 Inhibition
AU - Lee, Yuna
AU - Gu, Eun Ji
AU - Song, Ha Yeon
AU - Yoo, Bo Gyeong
AU - Park, Jung Eun
AU - Jeon, Jongho
AU - Byun, Eui Baek
N1 - Publisher Copyright:
© 2024 The Authors. Published by American Chemical Society.
PY - 2024/12/24
Y1 - 2024/12/24
N2 - Inducible cyclooxygenase-2 (COX-2) is a crucial enzyme involved in the processes of inflammation and carcinogenesis, primarily by catalyzing the production of prostaglandin E2 (PGE2), a significant mediator of inflammation. In this study, we designed and synthesized a series of novel chrysin derivatives to evaluate their anti-inflammatory potential through COX-2 inhibition using in vitro cultures of RAW264.7 macrophages and in silico molecular docking assays. Among the synthesized derivatives, compounds 1a and 8 demonstrated significant inhibition of lipopolysaccharide (LPS)-stimulated proinflammatory cytokine production, including interleukin-6 and tumor necrosis factor-alpha, in RAW264.7 cells. Additionally, these derivatives effectively inhibited PGE2 secretion through COX-2 enzyme inhibition in LPS-stimulated RAW264.7 cells. Molecular docking simulation results revealed that 1a and 8 possess high binding affinities for the COX-2 active site, indicating a strong potential for enzyme inhibition. Furthermore, druglikeness and ADMET predictions for these compounds indicated favorable pharmacokinetic properties, suggesting their suitability as drug candidates. Therefore, compounds 1a and 8 hold promise as potential anti-inflammatory agents for further development.
AB - Inducible cyclooxygenase-2 (COX-2) is a crucial enzyme involved in the processes of inflammation and carcinogenesis, primarily by catalyzing the production of prostaglandin E2 (PGE2), a significant mediator of inflammation. In this study, we designed and synthesized a series of novel chrysin derivatives to evaluate their anti-inflammatory potential through COX-2 inhibition using in vitro cultures of RAW264.7 macrophages and in silico molecular docking assays. Among the synthesized derivatives, compounds 1a and 8 demonstrated significant inhibition of lipopolysaccharide (LPS)-stimulated proinflammatory cytokine production, including interleukin-6 and tumor necrosis factor-alpha, in RAW264.7 cells. Additionally, these derivatives effectively inhibited PGE2 secretion through COX-2 enzyme inhibition in LPS-stimulated RAW264.7 cells. Molecular docking simulation results revealed that 1a and 8 possess high binding affinities for the COX-2 active site, indicating a strong potential for enzyme inhibition. Furthermore, druglikeness and ADMET predictions for these compounds indicated favorable pharmacokinetic properties, suggesting their suitability as drug candidates. Therefore, compounds 1a and 8 hold promise as potential anti-inflammatory agents for further development.
UR - http://www.scopus.com/inward/record.url?scp=85212984779&partnerID=8YFLogxK
U2 - 10.1021/acsomega.4c07938
DO - 10.1021/acsomega.4c07938
M3 - Article
AN - SCOPUS:85212984779
SN - 2470-1343
VL - 9
SP - 50491
EP - 50503
JO - ACS Omega
JF - ACS Omega
IS - 51
ER -