Influence of natural and synthetic compounds on cell surface expression of cell adhesion molecules, ICAM-1 and VCAM-1.
Various natural and synthetic compounds including alkaloids, terpenoids and phenolics were tested for inhibition of the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), both of which are crucial in the regulation of immune response and inflammation. Of 40 compounds tested, two compounds significantly downregulated the expression of VCAM-1 on murine endothelial cells (F-2) and ten compounds that of ICAM-1 on mouse myeloid leukemia cells (M1). Sanguinarine chloride (5) and isoliquiritigenin (13) were capable of lowering the levels of both ICAM-1 and VCAM-1. The structure-activity relationships study on chalcone and flavone derivatives related to 13 suggested that the inhibitory activity of the chalcone derivatives is attributable to the 4-hydroxy group as well as the possible coplanarity between the phenyl ring and the adjacent conjugated ketone.
Tanaka
S
S
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan. stanaka@nodai.ac.jp
Sakata
Y
Y
Morimoto
K
K
Tambe
Y
Y
Watanabe
Y
Y
Honda
G
G
Tabata
M
M
Oshima
T
T
Masuda
T
T
Umezawa
T
T
Shimada
M
M
Nagakura
N
N
Kamisako
W
W
Kashiwada
Y
Y
Ikeshiro
Y
Y
D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D053119:Benzophenanthridines; D002599:Chalcone / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D047188:Chalcones; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects*; D007546:Isoquinolines; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000302:isolation & purification / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects*
D000470:Alkaloids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053119:Benzophenanthridines; D047188:Chalcones; D007546:Isoquinolines; D010636:Phenols; D013729:Terpenes; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002599:Chalcone; C005705:sanguinarine; C040920:isoliquiritigenin