QSAR analysis of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole derivatives as selective COX-2 inhibitors.
Quantitative structure-activity relationship (QSAR) analysis was performed on a series of 1,3-diaryl-4,5,6,7-tetrahydro-2H-isoindole for their cyclooxygenase-2 (COX-2) inhibition. QSAR investigations were based on Hansch's extra thermodynamic multi-parameter approach and receptor surface analysis (RSA). QSAR investigations reveal that steric and electrostatic interactions are primarily responsible for COX-2 enzyme-ligand interaction. QSAR model derived from Hansch analysis demonstrated that COX-2 inhibitory activity is correlated with sum of atomic polarizability (Apol), number of hydrogen-bond donor groups (HBD), energy of the highest occupied molecular orbital (HOMO), desolvation free energy for water (F(H(2)O)) and fraction of areas of molecular shadow in the XY and ZX planes over area of enclosing rectangle (Sxyf and Sxzf) with r ranges 0.870-0.904. The best model was obtained from RSA model having r = 0.940 with good predictive ability (predicted compounds in training set and test set within +/- 1.0 unit of pIC(50)) and can be used in designing better selective COX-2 inhibitors among the congeners in future.
Silakari
Pratigya
P
Department of Chemistry, Dr HS Gour University, Madhya Pradesh, India.
Shrivastava
Savitri Devi
SD
Silakari
Gyati
G
Kohli
Dharm Veer
DV
Rambabu
Gundla
G
Srivastava
Soumya
S
Shrivastava
Santosh Kumar
SK
Silakari
Om
O
D051546:Cyclooxygenase 2 / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D051546:Cyclooxygenase 2