established, the mechanism by which /?-carotene exerts a protective function against cancer remains unknown. However, there are several lines of evidence which suggest that the generation of reactive oxygen species may play an important role in the development of cancer [14]. The present work emphasizes that attention should be extended from /?-carotene to lycopene and other carotenoids. Lycope...

The preclinical pharmacology and pharmacokinetic properties of (2R)-6-methoxy-8-(4-methylpiperazin-1-yl)-N-(4-morpholin-4-ylphenyl)chromane-2-carboxamide (AZD3783), a potent 5-hydroxytryptamine 1B (5-HT(1B)) receptor antagonist, were characterized as part of translational pharmacokinetic/pharmacodynamic hypothesis testing in human clinical trials. The affinity of AZD3783 to the 5-HT(1B) recepto...

Cl-secretion in the colon can be activated by an increase of either intracellular Ca2+ or cAMP. In this study we examined a possible interdependence of the two second-messenger pathways in human colonic epithelium. When measured in a modified Ussing chamber, carbachol (CCH; 100 μmol/l, basolateral), via an increase in cytosolic Ca2+concentration ([Ca2+]i), activated a transient lumen-negative e...

In the title compound, C41H31N3O3, the pyrazole and pyrrolidine rings adopt twisted conformations. The mean plane of the pyrazole ring forms dihedral angles of 9.11 (12) and 39.65 (11)° with the phenyl rings. The O atoms deviate from the mean planes of the chromene and ace-naphthyl-ene ring systems by 0.194 (15) and 0.079 (15) Å, respectively. In the crystal, molecules are linked via pairs of C...

1,1-Bis(3 -indolyl)-1-(p-substitutedphenyl)methanes (C-DIMs) containing para-trifluoromethyl, t-butyl, and phenyl groups are a novel class of peroxisome proliferator-activated receptor (PPAR) agonists. In LNCaP prostate cancer cells, these compounds induce PPAR -dependent transactivation, inhibit cell proliferation, and induce apoptosis. In addition, these PPAR agonists modulate a number of ant...

Suppression of malignant ventricular arrhythmias by selective blockade of the cardiac slowly activating delayed rectifier current (IKs) has been demonstrated with the benzodiazepine L-768673 [(R)-2-(2,4-trifluoromethyl-phenyl)-N-[2-oxo-5-phenyl-1-(2,2,2trifluoro-ethyl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]acetamide] in canine models of recent and healed myocardial infarction. The present s...