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.

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.

Optimum condition of Fourier transform infrared multiple-angle incidence resolution spectrometry for surface analysis.

A novel measurement technique of pure out-of-plane vibrational modes of thin films on a nonmetallic substrate has recently been proposed, which is named multiple-angle incidence resolution spectrometry (MAIRS). Since this technique could not be replaced by other conventional techniques, MAIRS was expected to be a promising tool for analysis of thin soft materials and surface adsorbates. Nevertheless, some experimental conditions have been found to be inappropriate for MAIRS, which yields incorrect results. In the present study, therefore, the problems in the technique have been investigated in terms of optics to improve the accomplishments of MAIRS. The problems have been found to have a strong relationship with optics in FT-IR, which is influenced by refractive index of the sample material and angle of incidence. In particular, optimization of the size matching of the detector surface and the infrared spot at the detector was a key to having MAIRS perform properly. It has been concluded that reliable MAIRS measurements require overfilling of the detector and a substrate with a high-refractive index.