A Comparative Multi-QSAR Modelling and Molecular Docking Studies of Some Arylsulfonamide-Based ADAM17 Inhibitors as Anticancer Agents
Posted: 10 Feb 2020
Date Written: February 7, 2020
Objective: ADAM17 is a zinc-dependent enzyme which is found to execute crucial roles in many threatening diseases such as inflammatory diseases, cancer, Alzheimer's disease and rheumatoid arthritis. Small molecule ADAM17 inhibitors may be valuable weapons in the wrestling against diseases.
Methods: A multi-QSAR modelling studies including 2D-QSAR, HQSAR, Bayesian classification, pharmacophore mapping and molecular docking studies of some arylsulfonamides were performed to explore the structural and pharmacophoric requirements of ADAM17 inhibitors.
Results: All these molecular modelling approaches were validated individually and these were statistically significant and reliable. Some pivotal structural and physicochemical molecular fingerprints that regulate ADAM17 inhibitory activity were identified. Moreover, the bulky steric and hydrophobic P1' substituents at the para position of the arylsulfonamido moiety favoured ADAM17 inhibition that supported and validated by molecular docking study. These crucial observations of arylsulfonamides may be considered for designing higher effective ADAM17 inhibitors in future.
Conclusions: These crucial observations of arylsulfonamides may be considered for designing higher effective ADAM17 inhibitors in future.
Keywords: Cancer, ADAM inhibitor, QSAR, arylsulfonamides, classification model, molecular docking
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