(+)-Corynoline

Bioorg Med Chem. 2005 Mar 1;13(5):1867-72.

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.[Pubmed: 15698804 ]

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.
METHODS AND RESULTS:
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).
CONCLUSIONS:
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.

Arch Pharm Res. 2002 Dec;25(6):817-9.

Inhibitory effect of corynoline isolated from the aerial parts of Corydalis incisa on the acetylcholinesterase.[Pubmed: 12510831]

METHODS AND RESULTS:
In the course of screening Korean natural products for acetylcholinesterase (AChE) inhibitory activity, it was found that a methanolic extract of the aerial parts of Corydalis incisa (Papaveraceae) showed significant inhibitory effects on AChE.
CONCLUSIONS:
Corynoline isolated from this plant inhibited AChE activity in a dose-dependent manner, and the IC50 value of corynoline was 30.6 microM. The AChE inhibitory activity of corynoline was reversible and noncompetitive.

Tetrahedron Letters Volume 27, Issue 19, 1986, Pages 2103–2106

Synthesis of a hypothetical intermediate in the biosynthesis of the 13-methylbenzophenanthridine alkaloids corynoline and 14-epicorynoline and the B-secoprotoberberine alkaloid corydalic acid methyl ester[Reference: WebLink]

A novel carbinolammonium chloride has been synthesized as a possible intermediate in the biosynthetic conversion of the 13-methylprotoberberine alkaloid (+)-tetrahydrocorysamine to the benzophenanthridine alkaloids (+)-Corynoline, (+)-14-epicorynoline, and the B-secoprotoberberine alkaloid (+)-corydalic acid methyl ester.