Inhibitory mode of 2-acetoxyphenyl alkyl sulfides against COX-1 and COX-2: QSAR analyses.
Selective inhibition of cyclooxygenase-2 (COX-2) inhibitors is an important strategy in design of potent anti-inflammatory compounds with significantly reduced side effects. Therefore, QSAR studies of 2-acetoxyphenyl alkyl sulfides were performed using Bioloom, CAChe 6.1, and Dragon 3.0 for the COX-2 and COX-1 inhibition. The analyses have produced good predictive and statistically significant QSAR models. These studies suggest that lipophilicity affects both COX-1 and COX-2 inhibition in different manner and indicator variables like presence of aromatic ring and triple bond play an important role in COX-2 selectivity. Branching in the molecule, higher path length 6 rich in polarizability, and lesser number of carbonyl groups would be favorable for COX-2 inhibition. Fourth highest eigenvalue of burden matrix corresponding to atomic mass would be favorable for COX-2 inhibition and sixth lowest eigenvalue of burden matrix corresponding to Sanderson electronegativities is conducive for COX-1 inhibition. Lower path length 3 rich in atomic mass and lesser degree of unsaturation in the molecule would be favorable for COX-1 inhibition.
Jain
Hemant Kumar
HK
Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar 470 003 (MP), India. hemantkjain2001@yahoo.co.in
Mourya
V K
VK
Agrawal
R K
RK
D000085:Acetates / Q000737:chemistry*; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008956:Models, Chemical; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013440:Sulfides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000085:Acetates; D016861:Cyclooxygenase Inhibitors; D013440:Sulfides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2