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

The 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) shows promise for its antinociceptive and anti-inflammatory properties. Here, we explored 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, alongside in silico analysis. Compounds a (-F), b (-CF3), c (-Bis-CF3), d (-CH3), e (-OOH), and 4-PSQ exhibited antinociceptive effects in chemical and thermal nociception models, except d (-CH3) and e (-OOH) in the hot plate test. None induced locomotor changes. In silico, only c (-Bis-CF3) showed low gastrointestinal absorption, and c (-Bis-CF3) and e (-OOH) lacked blood-brain barrier penetration, suggesting e (-OOH) lacked central antinociceptive effect. These compounds had higher COX-2 affinity than COX-1. Our findings suggest substituent insertion alters 4-PSQ's efficacy as an antinociceptive and anti-inflammatory agent.