title: Docking, CoMFA and CoMSIA studies of a series of sulfonamides derivatives as carbonic anhydrase I inhibitors.
abstract: 3D-QSAR methods, CoMFA region focusing (CoMFA-RF) and CoMSIA along with docking studies carried out for investigating 32 carbonic anhydrase I inhibitors. These inhibitors have been studied for the development of antiglaucoma, antitumor, antiobesity or anticonvulsant drugs. Docking analysis by GOLD provide conformations which have been realigned in CoMFA and CoMSIA models. Training set for the CoMFA-RF and CoMSIA models using 24 docked conformations gives q(2)(Loo) values of 0.615 and 0.637 and r(2)(nv) values of 0.701 and 0.713, respectively. The results of CoMFA-RF and CoMSIA with and without docked conformations were compared. The ability of prediction and robustness of the models were evaluated by test set, cross validation (leave-one-out and leave-ten-out), bootstrapping, and progressive scrambling approaches. The all-orientation search (AOS) was used to achieve the best orientation to minimize the effect of initial orientation of the structures. The docking results confirmed CoMFA and CoMSIA contour maps.
authors.affiliation: Chemistry Department, Faculty of Sciences, K. N. Toosi University of Technology, Tehran, Iran. Jahan.ghasemi@gmail.com
authors.forename: Jahan B
authors.initials: JB
authors.lastname: Ghasemi
authors.forename: Nastaran
authors.initials: N
authors.lastname: Meftahi
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000302:isolation & purification / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D020033:Protein Isoforms; D013449:Sulfonamides; D002256:Carbonic Anhydrases