QSAR Study on Some p-Arylthio Cinnamides as Antagonists of Biochemical ICAM-1/LFA-1 Interaction and ICAM-1/JY-8 Cell Adhesion in Relation to Anti-inflammatory Activity Original Research Article

In an attempt to find out the chemical and structural features of some p-arylthio cinnamides 1 as antagonists of biochemical ICAM-1/LFA-1 interaction as well as ICAM-1/JY-8 cell adhesion in relation to anti-inflammatory activity, QSAR study was performed. Steric effect on the arylthio ring and lipophilic substitutions at 2,3-positions, especially 2,3-disubstitution with Cl or CF3 or both on cinnamides 1 were conducive to the activity, whereas simultaneous presence of methoxy group at arylthio ring and NCOCH3 group at heterocyclic ring of cinnamides 1 were detrimental to activity in antagonism of biochemical ICAM-1/LFA-1 interaction. When inhibition of ICAM-1/JY-8 cell adhesion was considered, lipophilic substitution on ring B and simultaneous presence of CF3 groups at 2 and 3 positions of the ring B were advantageous to antagonism. This QSAR study showed that B ring has played the most important role for both types of activities. © 2002 Elsevier Science Ltd. All rights reserved.