title: Cell adhesion inhibitory activity of (d)-corynoline, a hexahydrobenzo[c]phenanthridine-type alkaloid, and its structure-activity relationship, studied by X-ray crystal structure analysis and molecular docking study.
abstract: Corynoline (1), a hexahydrobenzo[c]phenanthridine-type alkaloid, exhibited the concentration-dependent inhibition for the adhesion of human polymorphonuclear leukocyte and eosinophil to human umbilical vein cultured endothelial cell in the concentration range of showing no significant cytotoxicity for the cell: IC(50) value=72.4 microM for (d)-1 and 156.7 microM for (l)-1. This shows the potent anti-inflammatory and/or immunosuppressive activity of 1. To elucidate possible structure-activity relationship, the conformational/structural feature of (d)-1 was investigated by X-ray crystal structure analysis and molecular orbital energy calculations, and the docking study was performed for its interaction with the D1-domain of ICAM-1 (intracellular adhesion molecule-1). A plausible model was proposed, in which all polar atoms of (d)-1 are linked by hydrogen bonds or electrostatic interactions with the functional residues of ICAM-1, that have been supposed to be necessary for the binding with LFA-1 (leukocyte function-associated antigen-1). This suggests the potent inhibitory activity of 1 for the ICAM-1/LFA-1 adhesion and would be important on developing the clinically usable drugs for the inflammatory diseases.
authors.affiliation: Department of Physical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyama-kitamachi, Higashinada-ku, Kobe 658-8558, Japan. kamigami@kobepharma-u.ac.jp
authors.forename: Miyoko
authors.initials: M
authors.lastname: Kamigauchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Noda
authors.forename: Jujiro
authors.initials: J
authors.lastname: Nishijo
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Tobetto
authors.forename: Yasuko
authors.initials: Y
authors.lastname: In
authors.forename: Koji
authors.initials: K
authors.lastname: Tomoo
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishida
mesh_terms: D001600:Berberine Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D001600:Berberine Alkaloids; C487644:corynoline