Correlations between the rate constant of singlet oxygen quenching by imidazole derivatives and anti-inflammatory activity in rats
Bensasson, R.V.; Frederiksen, J.; Rougée, M.; Lexa, D.; Harrit, N.
Molecular Pharmacology 42(4): 718-722
1992
ISSN/ISBN: 0026-895X PMID: 1435748 Document Number: 391588
The second-order rate constants, k-DELTA, for quenching of molecular singlet oxygen O-2 (1-DELTA-g) by nonsteroidal anti-inflammatory imidazole drugs have been determined using time-resolved phosphorescence detection of singlet oxygen. A linear correlation was observed between log k-DELTA (ranging from 7.90 to 8.50) and the anti-inflammatory activity of these compounds (ranging from ED-50 = 15 to 300 mg/kg), as measured in rats by Jorgensen and Dyrsting (United States Patent 4,424,229 (1984)). The correlation between this physico-chemical parameter measured in vitro and a biological activity measured in vivo might be useful in screening other types of candidate anti-inflammatory drugs. The rate constant (k-DELTA) can be considered as a quantitative expression of the electron-donating power of the imidazole drug, as suggested by a correlation of log k-DELTA (ranging from 6.02 to 7.45) with Hammett substituent parameters observed in the case of 2-substituted imidazoles.