Synthesis and evaluation of analgesic, anti-asthmatic activity of (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 ones

Seventeen (E)-1-(8-hydroxyquinolin-7-yl)-3-phenylprop-2-en-1 one derivatives were synthesized via aldol condensation of substituted benzaldehydes with quinoline chalcones starting from 8-hydroxy quinoline. Molecular docking studies were performed on COX-2 protein for analgesic activity and PDE 4 enzyme for anti-asthmatic activity. Docking studies for analgesic activity reveal that the compounds 2, 4, 12, 14, and 15 showed significant interaction in terms of hydrogen bonding, hydrophobic attachment and van der Waal interaction with COX-2. The docking studies and pharmacological screening indicate that substitution of hydroxyl and conjugated ketone groups on the aldehyde ring and the quinoline ring accelerates analgesia with better binding to active site. Eddy's hot plate method was used to evaluate analgesic activity of the synthesized compounds. Compounds showed a substantial increase in reaction time when compared with standard pentazocin. Compounds 2, 4, 7, 9 and 13 showed significant binding interactions with PDE 4 enzyme and hence were selected for evaluation of anti-asthmatic activity using the goat tracheal chain method. Studies reveal that substitution of the methoxy group at 4th & 5th positions for compounds 2, 4 & 7 leads to significant percentage inhibition of histamine induced contraction. The synthesized compounds are thus found to be potent as analgesic and anti-asthmatic agents. 2014 The Authors. Production and hosting by Elsevier B.V.