Synthesis, molecular docking, molecular dynamics and ADMET prediction studies of novel (S)-Verbenone-Arylidene -Isoxazoline Hybrids

Abstract

The main objective of this work was to develop novel hybrid compounds from naturally occurring (S)-Verbenone. This last was used as a starting material to prepare new isoxazoline-verbenone-arylidene hybrids in two steps. All targeted compounds as well as their intermediates were fully characterized by 1H-, 13C-NMR and HRMS spectroscopic techniques. Then, a DFT study was carried out to understand the reactivity between the verbenone-arylidene as a source of two dipolarophiles with nitrile oxides. Finally, in silico molecular docking method was carried out to analyze the interactions of the prepared compounds with EGFR and Bcl-2 proteins. Moreover, the best-docked protein-ligand complexes was assessed using molecular dynamic simulation.