title: Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents.
abstract: Major anti-inflammatory agents, steroids and cyclooxygenase, were proved to have serious side effects. Here, a series of chalcone derivatives were synthesized and screened for anti-inflammatory activities. QSAR study revealed that the presence of electron-withdrawing groups in B-ring and electron-donating groups in A-ring of chalcones was important for inhibition of LPS-induced IL-6 expression. Further, compounds 22, 23, 26, 40, and 47 inhibited TNF-α and IL-6 release in a dose-dependent manner and decreased LPS-induced TNF-α, IL-1β, IL-6, IL-12, and COX-2 mRNA production. Mechanistically, compounds 23 and 26 interfered with JNK/NF-κB signaling and dose-dependently prevented ERK and p38 activation. In addition, 23 and 26 exhibited a significant protection against LPS-induced death and were able to block high glucose-activated cytokine profiles in macrophages. Together, these data show a series of anti-inflammatory chalcones with potential therapeutic effects in inflammatory diseases.
authors: School of Pharmacy, Wenzhou Medical College, Wenzhou, Zhejiang 325035, China.
authors: Jianzhang
authors: J
authors: Wu
authors: Jianling
authors: J
authors: Li
authors: Yuepiao
authors: Y
authors: Cai
authors: Yong
authors: Y
authors: Pan
authors: Faqing
authors: F
authors: Ye
authors: Yali
authors: Y
authors: Zhang
authors: Yunjie
authors: Y
authors: Zhao
authors: Shulin
authors: S
authors: Yang
authors: Xiaokun
authors: X
authors: Li
authors: Guang
authors: G
authors: Liang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000502:physiology; D021281:Quantitative Structure-Activity Relationship; D012333:RNA, Messenger / Q000096:biosynthesis; D012772:Shock, Septic / Q000188:drug therapy; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism; D016019:Survival Analysis; D014158:Transcription, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C570406:2-chloro-4'-methoxychalcone; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047188:Chalcones; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D005947:Glucose