QSPR analysis to predict some quantum chemical properties of 2‐phenylindol derivatives as anticancer drugs using molecular descriptor and genetic algorithm multiple linear regression

Abstract

AbstractThermodynamic properties of molecules provide fundamental information for binding in fragment‐based drug discovery programs and for understanding complex interactions. Experimental measurements of some thermodynamic properties are not always feasible. Quantum mechanical methods and group contribution methods are the major toolboxes to obtain some theoretical quantities. In drug discovery and development, computational studies can reduce the costs and risks of bringing a new medicine to market. Computational methods have been widely used to optimize promising new ligands by estimating their binding affinity to proteins using the thermodynamic ligand binding parameters (Gibbs energy, enthalpy, entropy, and heat capacity). In this article, the relationship between molecular descriptors and quantum chemical properties, such as the Gibbs free energy (ΔG kJ mol−1) and enthalpy of formation (ΔHf kJ mol−1) of 2‐phenylindole derivatives as anticancer drugs is studied. These properties were calculated at the DFT‐B3LYP/6‐311G (d,p) level of quantum chemistry by Gaussian 09 software. Molecular descriptors were calculated by Dragon 5.4 software, and the stepwise multiple linear regression (MLR) and the Genetic algorithm (GA) techniques were used to select the best descriptors and build QSPR models. To evaluate the predictive ability of developed quantitative structure‐property relationship (QSPR) models, different internal and external validation methods were adopted. The predictive powers of the models were found to be satisfactory. The models revealed that 3D matrix‐based descriptors (H3D, SEig) are useful to predict the Gibbs free energy and enthalpy of formation of the investigated compounds respectively.