Rational design, synthesis, and pharmacological properties of pyranochalcone derivatives as potent anti-inflammatory agents.
24 derivatives (5a-x) derived from natural pyranochalcones (I and II) were designed and evaluated for their inhibitory potency on the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells. Among them, four compounds (5b, 5d, 5f, and 5h) exhibited more potent inhibitory effects on iNOS activity and iNOS-mediated NO production than a positive control indomethacin. Furthermore, 5b could significantly suppress the progression of carrageenan-induced hind paw edema compared to indomethacin at a dosage of 10 mg/kg/day, and dose-dependently ameliorated the development of adjuvant-induced arthritis (AIA) validated by arthritic scores and H&E staining of joints. In addition, docking study confirmed that 5b was an iNOS inhibitor with binding to the active site of murine iNOS.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
Fei
F
Peng
Guangcheng
G
Wang
Xiuxia
X
Li
Dong
D
Cao
Zhuang
Z
Yang
Liang
L
Ma
Haoyu
H
Ye
Xiaolin
X
Liang
Yan
Y
Ran
Jinying
J
Chen
Jingxiang
J
Qiu
Caifeng
C
Xie
Chongyang
C
Deng
Mingli
M
Xiang
Aihua
A
Peng
Yuquan
Y
Wei
Lijuan
L
Chen
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D002351:Carrageenan / Q000494:pharmacology; D020134:Catalytic Domain; D002460:Cell Line; D002599:Chalcone / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D047188:Chalcones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D001578:Benzopyrans; D047188:Chalcones; D002599:Chalcone; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II