Oxidative functionalization of triterpenes isolated from Euphorbia resinifera latex: Semisynthesis, ADME-Tox, molecular docking, and molecular dynamics simulations

Abstract

Natural triterpenes isolated from Euphorbia resinifera latex, α-Euphol and α- Euphorbol, have been subjected to structural modification using oxidative agents such as chromic anhydride (CrO3) and sodium periodate in the presence of ruthenium trichloride NaIO4-(RuCl3, 3H2O) to obtain new triterpene derivatives with good yield. The semi-synthesized triterpenes (1-9) and (10-16) prepared from α-Euphol and α-Euphorbol have been tested in silico to predict and evaluate their antibacterial and insecticidal properties. Among the tested compounds, three of them (3, 15, and 16) were discarded after evaluating their drug-likeness and ADME-Tox profiles. Then, a molecular docking analysis was performed to predict which one of the studied compounds could inhibit MurE (PDB ID: 1E8C) and EcR (PDB ID: 1R20) proteins involved in antibacterial and insecticidal activities, respectively. Among the docked compounds, only compounds 8 and 9 showed better stability in the MurE and EcR receptor pocket than the Amoxicillin and 20-Hydroxyecdysone used as standards. After that, molecular dynamics simulation was performed to further investigate the stability of compound 9 in the binding pocket of both targeted receptors. Eventually, the outcomes of this study show that the new triterpene derivative 9 could be used as a promising candidate to develop new insecticides and antibacterial drugs.