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

•A series of natural bioactive (S)-Verbenone-izoxazoline (7a-d) were synthesized.•Synthetic compounds are characterized by spectroscopic techniques (1H- & 13C- NMR) and HRMS.•Chemical reactivity and chemical stability parameters were observed via density funtional theory calculations.•Molecular docking studies revealed that compound 7a showed the most favorable docking score (−9.5 kcal/mol towards Bcl2 and −9.5 kcal/mol towards EGFR).•Docking results were supported by molecular dynamic simulations. 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-, 13CNMR 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. [Display omitted]