3D-QSAR, Molecular Docking and ADMET Studies of Benzothiadiazinonedioxides-Triazole Derivatives Against Carbonic Anhydrase-XII

A series of novel 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one-1,1-dioxides(BTDs) as hCA XII inhibitors with remarkable activities have been reported recently. In this study, a three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking, ADMET and drug-likeness analyses were conducted on the reported BTDs to gain deeper insight into the key pharmacological features of hCA XII inhibitors and identify new potential compounds. The constructed 3D-QSAR models demonstrated reliable predictability with satisfactory validation parameters. Including Q2 = 0.660, R2 = 0.957 and R2pred = 0.701 in CoMFA model, and Q2 = 0.685, R2 = 0.969 with R2pred = 0.829 in CoMSIA model. Molecular docking provides further insights into the binding modes of these BTDs with the CA XII protein. The results indicated that key residues Thr199, Thr200, Gln92, Asn62 and Leu198 could interact with BTDs by hydrogen bonds or hydrophobic interactions, which might be significant for the activity. The information obtained will be very helpful for designing new derivatives with high anti-hCA XII activity.