1-(2,3,4-trimethoxyphenyl)-3-(3-(2-chloroquinolinyl))-2-propen-1-one, a chalcone derivative with analgesic, anti-inflammatory and immunomodulatory properties.
OBJECTIVE
The synthetic chalcone derivative 1-(2,3,4-trimethoxyphenyl)-3-(3-(2-chloroquinolinyl))-2-propen-1-one (TQ) was evaluated for its immunomodulatory and anti-inflammatory efficacy in vitro and in vivo.


METHODS
Human neutrophils and lymphocytes from healthy volunteers and RAW 264.7 murine macrophages. Swiss mice and Lewis rats were randomly divided into groups of six animals.


METHODS
TQ was orally administered in all in vivo assays (10-30 mg/kg).


METHODS
Elastase, superoxide and LTB(4) release were assayed in human neutrophils, NO/PGE(2) production and NF-kappaB activation in RAW 264.7, and (3)H thymidine incorporation in human lymphocytes. Zymosan-stimulated air pouches, DNFB-DTH, PBQ-induced writhings and formalin-induced pain were assayed in mice. Adjuvant-induced arthritis was tested in rats. Dunnett's t-test was employed for statistical analysis.


RESULTS
Human T-cell proliferation, neutrophil functions and NO/PGE(2) production in murine macrophages were inhibited by TQ (IC(50) in the microM range), which showed anti-inflammatory, immunomodulatory and analgesic effects.


CONCLUSIONS
Our findings indicate the potential interest of TQ in the modulation of some immune and inflammatory responses probably by NF-kappaB inhibition.
De León
E J
EJ
Department of Pharmacology, University of Valencia, Faculty of Pharmacy, Av Vicent Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Alcaraz
M J
MJ
Dominguez
J N
JN
Charris
J
J
Terencio
M C
MC
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D015153:Blotting, Western; D002455:Cell Division; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology*; D047188:Chalcones; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000188:drug therapy; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007527:Isoenzymes / Q000096:biosynthesis; D019272:Leukocyte Elastase / Q000378:metabolism; D007975:Leukotriene B4 / Q000096:biosynthesis; D008163:Luminescent Measurements; D008213:Lymphocyte Activation / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects; D008565:Membrane Proteins; D051379:Mice; D018375:Neutrophil Activation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D010741:Phospholipases A / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011804:Quinolines / Q000494:pharmacology*
C482649:1-(2,3,4-trimethoxyphenyl)-3-(3-(2-chloroquinolinyl))-2-propen-1-one; D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047188:Chalcones; D007202:Indicators and Reagents; D007527:Isoenzymes; D008565:Membrane Proteins; D009573:Nitrites; D011804:Quinolines; D007975:Leukotriene B4; D002599:Chalcone; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D010741:Phospholipases A; D019272:Leukocyte Elastase; D015232:Dinoprostone