Application of Physicochemical and DFT Based Descriptors for QSAR Study of Camptothecin Derivatives

Abstract

AbstractDensity functional based reactivity descriptors such as electrophilicity (ω), Fukui functions ( , ), energies of LUMO and next LUMO along with the physicochemical parameters (logP, hydration energy, molar refractivity and surface area) are introduced for QSAR studies of two different sets of camptothecin molecules. A good correlation between the biological activity and the DFT based descriptors is obtained using multiple linear regression analysis. In literature, the importance of the various classic 2D descriptors such as logP, molar refractivity (MR), surface area has been greatly emphasize but in this report we have focused mainly on the importance of the DFT based reactivity descriptors in understanding the behaviors of campothecins. The modeled QSAR equations derived by regression analysis predicted that the camptothecin inhibitory activity is highly correlated with the DFT‐based descriptors such as fukui functions, lowest unoccupied molecular orbital (ELUMO), hydration energy and solvent accessible surface area of the molecules.