QSAR and molecular docking study of quinazoline derivatives as anticancer agents using molecular descriptors. (2022)

• Record Type: Journal Article
• Authors: Kasmi, R.; Hadaji, E.; Bouachrine, M.; Ouammou, A.
• Is Part Of: Materials today. Volume 51:Part 5(2022)
• Page Start: 1821
• Page End: 1830
• Publication Date: 2022
• Subjects: QSAR -- Anti-cancer -- MLR -- MNLR -- Cross-validation (CV) -- Y-randomization -- Molecular Docking; Materials science -- Congresses -- Periodicals; 620.1
• DOI: 10.1016/j.matpr.2020.05.283
• Languages: English
• ISSNs: 2214-7853

Abstract

Abstract: Much of the in-silico research in the world has been directed towards rational drug design, environmental risk assessment, toxicity and the forecasting of the characteristics of chemical and pharmaceutical products. The aim of this study was conceived to suggest a 2D-QSAR study of a new series of 26 quinazoline derivatives, acting as antitumor agents by the DFT-B3LYP method with the 6 31G base set. The starting point for such methods is built on the definition of chemical descriptors that accurately reflect the most precise details of molecular structures imported from an experimental reference database. In order to analyze structural data and detect the determining factors for anticancer activity, different types of tools can be used: multiple linear (MLR) and non-linear (MNLR) regressions, principal component regression PCA and partial least square (PLS) regression. The 3 models MLR, MNLR and PLS were developed and validated on a training set of 20 molecules, their robustness is estimated by internal validation methods and their predictive power was assessed by external validation from a set of 6 molecules with predicted correlation coefficients Rtest of 0.93, 0.94 and 0.94 respectively. In this work, 4 relevant descriptors that can influence the anti-cancer activity, specifically the lowest unoccupied molecular orbital energy, dipole moment, surface tension and the number of H-bond donors. Therefore, on the basis of these descriptors, new molecules belonging to the same structures have been theoretically designed. This work also consists in studying the inhibition of tyrosine kinase activity over expressed by quinazoline derivatives with molecular docking which is one of the molecular modeling methods.