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.
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 CF(3) or both on cinnamides 1 were conducive to the activity, whereas simultaneous presence of methoxy group at arylthio ring and NCOCH(3) 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 CF(3) 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.
Debnath
Bikash
B
Division of Pharmaceutical and Medicinal Chemistry, Department of Pharmaceutical Technology, PO Box 17020, Jadavpur University, Kolkata 700 032, India.
Samanta
Soma
S
Roy
Kunal
K
Jha
Tarun
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002934:Cinnamates / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001555:Benzene Derivatives; D002934:Cinnamates; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1