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Res Pharm Sci. 2016 Dec;11(6):445-453. doi: 10.4103/1735-5362.194869.

A quantitative structure-activity relationship (QSAR) study of some diaryl urea derivatives of B-RAF inhibitors.

Author information

1
Department of Medicinal Chemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
2
Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, I.R. Iran.
3
Department of Medicinal Chemistry and Novel Drug Delivery Systems Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Abstract

In the current study, both ligand-based molecular docking and receptor-based quantitative structure activity relationships (QSAR) modeling were performed on 35 diaryl urea derivative inhibitors of V600EB-RAF. In this QSAR study, a linear (multiple linear regressions) and a nonlinear (partial least squares least squares support vector machine (PLS-LS-SVM)) were used and compared. The predictive quality of the QSAR models was tested for an external set of 31 compounds, randomly chosen out of 35 compounds. The results revealed the more predictive ability of PLS-LS-SVM in analysis of compounds with urea structure. The selected descriptors indicated that size, degree of branching, aromaticity, and polarizability affected the inhibition activity of these inhibitors. Furthermore, molecular docking was carried out to study the binding mode of the compounds. Docking analysis indicated some essential H-bonding and orientations of the molecules in the active site.

KEYWORDS:

B-RAF inhibitors; Diaryl Urea; Docking; Multiple linear regressions; PLS-LS-SVM; QSAR

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