title: Synthesis and anti-inflammatory activity of paeonol analogues in the murine model of complete Freund's adjuvant induced arthritis.
abstract: A new series of paeonol alkyl ether analogues were synthesized and confirmed with IR,1H NMR,13C NMR and HRMS spectra. They have shown anti-inflammatory activities by scavenging mediator of free radicals and inhibiting lipid mediator of inflammation on complete Freund's adjuvant (CFA) induced arthritis in mice. The in vitro and in vivo scavenging ability of free radicals was determined by using chemical analysis and commercial assay kits, respectively. The in vivo inhibiting lipid mediator of inflammation was examined by ELISA. Our results indicated that the substitution of the hydrogen in hydroxyl group at C2position of paeonol 1 by short carbon chain, in the presence or absence of bromo atom at C5position, decreased its scavenging ability on radicals (3a or 4a vs 1), while the long alkyl substitution (Cn>14) increased the activity. Compared with 3a or 4a, scavenging abilities of 3a-h or 4a-h gradually increased following the length elongation of alkyl carbon chain. Compounds 3h and 4h showed great scavenging ability on OH, O2-, DPPH, ATBS+and MDA, and good promotion on T-AOC and SOD. The results of the in vivo inhibiting lipid mediator of inflammation also demonstrated that 3h, 4h exhibited substantial inhibition on enzyme activity of COX-2, PGE2. Therefore, 3h and 4h have great potential to be the novel anti-inflammatory drug candidates for the therapy of arthritis.
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
authors.forename: Ligua
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China. Electronic address: zbs360@swu.edu.cn.
authors.forename: Baoshun
authors.initials: B
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Southwest University, Chongqing 400716, PR China.
authors.forename: You
authors.initials: Y
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, PR China.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Gong
authors.affiliation: Chongqing Institute for Food and Drug Control, Chongqing 401211, PR China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Chongqing Institute for Food and Drug Control, Chongqing 401211, PR China.
authors.forename: Zhenxu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Ninth People's Hospital of Chongqing, Chongqing 400700, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: The Ninth People's Hospital of Chongqing, Chongqing 400700, PR China.
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005620:Freund's Adjuvant / Q000008:administration & dosage*; D051379:Mice; D013057:Spectrum Analysis / Q000379:methods
chemical_list: D000098:Acetophenones; C013638:paeonol; D005620:Freund's Adjuvant; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory; Cyclooxygenase-2; Free radicals; Paeonol analogues