Correlations between the rate constant of singlet oxygen quenching by imidazole derivatives and anti-inflammatory activity in rats.
The second-order rate constants, k delta, for quenching of molecular singlet oxygen O2 (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 ED50 = 15 to 300 mg/kg), as measured in rats by Jørgensen 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 deta (ranging from 6.02 to 7.45) with Hammett substituent parameters observed in the case of 2-substituted imidazoles.
Bensasson
R V
RV
Laboratoire de Biophysique, CNRS URA 481, INSERM U201, Paris, France.
Frederiksen
J
J
Rougée
M
M
Lexa
D
D
Harrit
N
N
D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007093:Imidazoles; D005461:Fluorine; D010100:Oxygen