Semisynthesis of new isoxazolines from (E)-α-atlantone: Antibacterial, antifungal activities, ADME-Tox, molecular docking, and molecular dynamics simulations investigations

Abstract

In the present work, new isoxazolines were semisynthesized by 1,3-dipolar cycloaddition reactions of nitriloxides on (E)-α-atlantone, a sesquiterpene compound isolated from Cedrus atlantica essential oil. The reaction proceeds in a chemo- and periselective manner to lead to two cycloadducts 3 and 3′. The structures of the obtained cycloadducts were determined using infrared, nuclear magnetic resonance spectroscopy, high resolution mass spectrometry, and elemental analysis. In addition, the semisynthesized cycloadducts were screened for their antimicrobial antibacterial and antifungal activities which they show significant diameter of inhibition zones ranging from 9 to 41.5 mm against Staphylococcus aureus, Proteus mirabilis, and Candida albicans. Furthermore, in silico investigations were conducted employing molecular docking, molecular dynamics, and (absorption, distribution, metabolism, excretion, toxicity) tests as well as drug-likeness evaluation, to complement the experimental findings and enhance our understanding of the potential bioactivity of the compounds at the molecular level.