Structure-Activity Relationship of 7-Chloro-4-(Phenylselanyl) Quinoline: Novel Antinociceptive and Anti-Inflammatory Effects in Mice.

Abstract

The 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) stands out for its potential antinociceptive and anti-inflammatory activities. Thus, in this study we investigated the structure-activity relationship of 4-PSQ and its analogues 7-chloro-4-[(4-fluorophenyl) selanyl]quinoline (a), 7-chloro-4-{[3-trifluoromethyl)phenyl] selanyl}quinoline (b), 4-((3,5-Bis(trifluoromethyl)phenyl)selanyl-7-chloroquinoline (c), 7-chloro-4-[(2,4,6-trimethyl)selanyl]quinolinic acid (d) and 7-chloroquinoline-4-selenium acid (e) in models of acute inflammation and chemical, thermal and mechanical nociception in mice, as well as by in silico methods. The compoundsa(-F),b(-CF3),c(-Bis-CF3),d(-CH3),e(-OOH) and 4-PSQ exert antinociceptive effects in chemical and thermal nociception models, except compoundsd(-CH3) ande(-OOH) that did not show antinociceptive effects in the hot plate test. In addition, treatments with all compounds did not cause locomotor changes in mice. In silico datathe compounds revealed that only compoundc(Bis-CF3) exhibited low gastrointestinal absorption and that compoundsc(Bis-CF3) ande(-OOH) do not have the ability to penetrate the blood-brain barrier, indicating that compounde(-OOH) did not produce a central antinociceptive effect. Furthermore, we found that this class of compounds has a higher affinity for COX-2 than for COX-1. In general, our data indicate that the insertion of substituents can alter the efficiency of 4-PSQ as an antinociceptive and anti-inflammatory agent.