DFT investigations on conformational analysis, solvation effects, reactivity studies, chemical descriptors and docking of two anti‐cancerous drugs, Lenvatinib and Regorafenib

Abstract

AbstractTwo anticancer drugs, lenvatinib (LNTB) and regorafenib (RGFB) are evaluated for their solvent effects, wavefunction reactivity properties and different chemical descriptors by means of theoretical methods. Potential energy surface scan studies about all possible rotable bonds are performed and lowest energy conformations of LNTB and RGFB are for the torsion angles C25‐C24‐C29‐N9 and C25‐N10‐C15‐C21. Reactive sites are O and N, H atoms, giving nucleophilic and electrophilic attacks for both the molecules. Solvation free energies are calculated in different solvents and all solvents are suitble except heptane. Electron densities of LNTB and RGFB show that closed‐shell interactions are in different regions. The intramolecular hydrogen bonds of the compounds LNTB and RGFB are found at O2‐H38, Cl1‐H37 & O5‐H47 and F2‐H38, N11‐H45, O7‐H35 & O7‐H37, respectively. Due to anticancer activities, LNTB and RGFB are docked with different proteins which give binding affinities from ‐8.4 to ‐10.5 for RGFB and ‐7.9 to ‐10.1 kcal/mol for LNTB.