Inhibition of immune complex-mediated neutrophil oxidative metabolism: A pharmacophore model for 3-phenylcoumarin derivatives using GRIND-based 3D-QSAR and 2D-QSAR procedures

In this study, twenty hydroxylated and acetoxylated 3-phenylcoumarin derivatives were evaluated as inhibitors of immune complex-stimulated neutrophil oxidative metabolism and possible modulators of the inflammatory tissue damage found in type III hypersensitivity reactions. By using lucigenin- and luminol-enhanced chemiluminescence assays (CL-luc and CL-lum, respectively), we found that the 6,7-dihydroxylated and 6,7-diacetoxylated 3-phenylcoumarin derivatives were the most effective inhibitors. Different structural features of the other compounds determined CL-luc and/or CL-lum inhibition. The 2D-QSAR analysis suggested the importance of hydrophobic contributions to explain these effects. In addition, a statistically significant 3D-QSAR model built applying GRIND descriptors allowed us to propose a virtual receptor site considering pharmacophoric regions and mutual distances. Furthermore, the 3-phenylcoumarins studied were not toxic to neutrophils under the assessed conditions. (C) 2007 Elsevier Masson SAS. All rights reserved.

Group outside the Sub Inspector Office during Ky visit

Group of people outside the Sub Inspector Office during visit of former South Vietnamese vice president Nguyen Cao Ky to Brisbane, Australia in January 1967.

Street elevation, Office and Shops Boroko

As seen from adjacent street corner.

Street elevation, Office and Shops Boroko

As seen from road.

Side elevation, Office and Shops Boroko

As seen from adjacent block.

Warehouse, PNG Coffee Industry Board Office and Warehouse, Goroka

View of exterior wall to warehouse.

Downpipes, PNG Coffee Industry Board Office and Warehouse, Goroka

Detailed view of downpipes and drainage grill.

PNG Coffee Industry Board Office and Warehouse, Goroka

View past tiered amphitheatre and offices above to air strip beyond.

View along western elevation, PNG Coffee Industry Board Office and Warehouse, Goroka

View past timber blinds to balcony and timber sunscreens.

Under construction, PNG Coffee Industry Board Office and Warehouse, Goroka

View of post being hoisted into position during construction.

Warehouse, PNG Coffee Industry Board Office and Warehouse, Goroka

View of warehouse exterior.

Pole detail, PNG Coffee Industry Board Office and Warehouse, Goroka

Detailed view of poles used in construction. Poles were spliced in their length with steel bars (like 3 pin plugs) and these joints were restrained from splitting with steel strap belts. The belts were tightened with opposing wedges like the old Greene & Greene wrought iron detail.

Warehouse, PNG Coffee Industry Board Office and Warehouse, Goroka

View of warehouse exterior.