title: Anthranilate derivatives as TACE inhibitors: docking based CoMFA and CoMSIA analyses.
abstract: Anthranilic acid based derivatives (ANTs) have been identified as a novel class of potent tumor necrosis factor-α converting enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses has been performed to elucidate the atomic details of the TACE/ANT interactions and also to identify the most important features impacting TACE inhibitory activity of ANTs. The CoMSIA model resulted to be slightly more predictive than CoMFA model, and gave conventional r² 0.991, r²(cv) 0.793, q² 0.777, SEE 0.050, F-value 655.610, and r²(test) 0.871. The 3D-QSAR field contributions and the structural features of the TACE binding site showed a good correlation. These studies will be useful to design new TACE inhibitors with improved potency.
authors.affiliation: Department of Pharmaceutical Science and Drug Research, Punjabi University, Patiala, Punjab 147002, India.
authors.forename: Malkeet Singh
authors.initials: MS
authors.lastname: Bahia
authors.forename: Shravan Kumar
authors.initials: SK
authors.lastname: Gunda
authors.forename: Shwetha Reddy
authors.initials: SR
authors.lastname: Gade
authors.forename: Saikh
authors.initials: S
authors.lastname: Mahmood
authors.forename: Ravikumar
authors.initials: R
authors.lastname: Muttineni
authors.forename: Om
authors.initials: O
authors.lastname: Silakari
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors*; D000072198:ADAM17 Protein; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D004791:Enzyme Inhibitors; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D051722:ADAM Proteins; D000072198:ADAM17 Protein