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

Journal of Enzyme Inhibition and Medicinal Chemistry

Ali Akbar Saboury¹  Claudiu T. Supuran²  Jahan Ghasemi³  Yeganeh Entezari Heravi³  Hassan Sereshti³  Marzieh Amirmostofian⁴ 

[1] Institute of Biochemistry and Biophysics, University of Tehran;Universita degli Studi di Firenze;University of Tehran;Zabol University of Medical Sciences;

关键词: Carbonic anhydrase isoform II;    molecular docking;    pharmacophore;    sulfonamide;    virtual screening;   

DOI  :  10.1080/14756366.2016.1241781

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown