DFT Conformational, Wavefunction Based Reactivity Analysis, Docking and MD Simulations of a Carboxamide Derivative with Potential Anticancer Activity

The aim of this article is to use electronic structure approaches to investigate the chemical characteristics of <i>N</i>-[2-(diethylamino)ethyl]-5-[(<i>Z</i>)- (5-fluoro-2-oxo-1<i>H</i>-indol-3-ylidene) methyl] − 2,4-dimethyl-1<i>H</i>-pyrrole-3-carboxamide (Sunitinib) (DFDC), a carboxamide derivative with antitumor activity. For the dihedral angle of C13-C9-C16-N6 (160.0°) of DFDC, conformational analysis predicted the lowest energy conformer. Except for heptane, UV absorptions in various solvents and air give nearly identical. The hydrogen atom for which electron density exceeds upper limit of the color scale in localized orbital locator (LOL) analysis, whereas the blue color circles around the selected atoms in DFDC are for oxygen, and there are few carbon atoms with the electron depleted regions between inner and outer valence regions in DFDC. The biological impacts of the reactivity descriptors were addressed. Studies of wavefunction dependent properties such as LOL, electron localization function (ELF), and others provide a wealth of knowledge on electronic properties that is sufficient for predicting the bioactivity. Docking is done with several PDBs due to the anticancer activity of DFDC and bovine serum albumin corresponding to 3V03 yields the highest binding energy and MD simulations of DFDC with 3V03 are investigated in detail.