title: Design, synthesis and anti-inflammatory evaluation of novel 5-benzylidene-3,4-dihalo-furan-2-one derivatives.
abstract: Rosiglitazone has shown promising anti-inflammation effect. To develop preferable anti-inflammatory agents, twenty-two rosiglitazone analogs were synthesized and their anti-inflammatory activity was evaluated. Among these compounds, 6i and 6k displayed excellent inhibitory activities on the production of inflammatory mediators, including nitric oxide (NO), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Furthermore, 6i and 6k showed suppression effects on the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, and this suppression effects could be partially reversed by GW9662, which is a peroxisome proliferator-activated receptor γ (PPARγ) antagonist. Additionally, our docking results exhibited the well combination of 6i and 6k to PPARγ. So the anti-inflammation activity of 6i and 6k was due at least in part, to their interaction with PPARγ.
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China.
authors: Fang
authors: F
authors: Wang
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China.
authors: Jun-Rong
authors: JR
authors: Sun
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China.
authors: Mei-Yan
authors: MY
authors: Huang
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China.
authors: Hui-Ying
authors: HY
authors: Wang
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China.
authors: Ping-Hua
authors: PH
authors: Sun
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China.
authors: Jing
authors: J
authors: Lin
authors: Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Huangpu Dadao West, Guangzhou 510632, PR China. Electronic address: twmchen@jnu.edu.cn.
authors: Wei-Min
authors: WM
authors: Chen
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D015195:Drug Design; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000093242:Interleukin-6 Inhibitors
chemical_list: D000813:Anilides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001597:Benzylidene Compounds; D005663:Furans; D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D009569:Nitric Oxide; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C457499:2-chloro-5-nitrobenzanilide
keywords: 3,4-Dihalo-furan-2-one; ABANBEMMKJDTOF-PTNGSMBKSA-N; AMJIFQUYNVDTFW-IUXPMGMMSA-N; Action mechanism; Anti-inflammation; CHJVOYRHJNNIMW-YBEGLDIGSA-N; CIOUHMMWGSCAGE-BOPFTXTBSA-N; CXIOINFZWKMBRE-PXNMLYILSA-N; FHKOJWSHWJJAGD-YBEGLDIGSA-N; FKOSYLLHVHNTSB-WQRHYEAKSA-N; IVHUDKIIJMQQPF-PXNMLYILSA-N; JNMWXEAYOCCTNX-ZROIWOOFSA-N; JTLWBBCUDCJUMW-IUXPMGMMSA-N; KAFDGUUQEAQRRD-WJDWOHSUSA-N; LGZKLGBJPAHGJM-NVMNQCDNSA-N; LZGWJKGHJBSCEQ-UNOMPAQXSA-N; MHQROZUURSCCLO-ATVHPVEESA-N; NXVJMBQJUQBQJO-ATVHPVEESA-N; PPARγ; QRNWQFRSONLXNU-ZROIWOOFSA-N; QWIPTCMHCFLGIV-WJDWOHSUSA-N; RWIGBEAPQKJRPF-BOPFTXTBSA-N; Synthesis; TVOYMUJQDNCTLS-DHDCSXOGSA-N; WSYCMIWDSXXXAD-DHDCSXOGSA-N; YJWGLMMFJLJYGT-PXNMLYILSA-N; YJYLUYMSVPTCOU-PTNGSMBKSA-N