3D QSAR studies, pharmacophore modeling, and virtual screening of diarylpyrazole-benzenesulfonamide derivatives as a template to obtain new inhibitors, using human carbonic anhydrase II as a model protein.
A 3D-QSAR modeling was performed on a series of diarylpyrazole-benzenesulfonamide derivatives acting as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The compounds were collected from two datasets with the same scaffold, and utilized as a template for a new pharmacophore model to screen the ZINC database of commercially available derivatives. The datasets were divided into training, test, and validation sets. As the first step, comparative molecular field analysis (CoMFA), CoMFA region focusing and comparative molecular similarity indices analysis (CoMSIA) in parallel with docking studies were applied to a set of 41 human (h) CA II inhibitors. The validity and the prediction capacity of the resulting models were evaluated by leave-one-out (LOO) cross-validation approach. The reliability of the model for the prediction of possibly new CA inhibitors was also tested.
a Department of Chemistry, Faculty of Science , University of Tehran , Tehran , Iran.
Yeganeh
Y
Entezari Heravi
a Department of Chemistry, Faculty of Science , University of Tehran , Tehran , Iran.
Hassan
H
Sereshti
b Institute of Biochemistry and Biophysics, University of Tehran , Tehran , Iran.
Ali Akbar
AA
Saboury
a Department of Chemistry, Faculty of Science , University of Tehran , Tehran , Iran.
Jahan
J
Ghasemi
c Department of Medicinal Chemistry, School of Pharmacy , Zabol University of Medical Sciences , Zabol , Iran.
Marzieh
M
Amirmostofian
d Dipartimento Neurofarba , Universita degli Studi di Firenze , Sezione di Scienze Farmaceutiche , Florence , Sesto Fiorentino , Italy.
Claudiu T
CT
Supuran
D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D024402:Carbonic Anhydrase II; D002257:Carbonic Anhydrase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000096926:Benzenesulfonamides
Carbonic anhydrase isoform II; molecular docking; pharmacophore; sulfonamide; virtual screening