Mechanism and stereoselectivity of epoxidation reaction of a β-himachalene derivative: Insights from DFT, molecular docking, ADMET, and molecular dynamics investigations

• Published in: Journal of molecular structure 2025-01, Vol.1320, p.139664, Article 139664
• Main Authors: Rossafi, Bouchra, Outahar, Fatima, Hammoudan, Imad, Moumou, Mohamed, Touti, Rodouan, Benharref, Ahmed, Chtita, Samir
• Format: Article
• Language: English
• Subjects: ADMET; DFT/B3LYP/6-31G(d); Epoxidation; m-CPBA, Antidiabetic activity; Molecular docking; Molecular dynamics
• ISSN: 0022-2860
• DOI: 10.1016/j.molstruc.2024.139664

•Epoxidation of compound A with m-CPBA produces P1 and P2 epoxides, modifying the C9=C10 double bond.•Computational DFT/B3LYP/6-31G(d) studies confirm the reaction's exothermic nature and high stereoselectivity, favoring P1 formation as seen in experiments.•IRC calculations indicate a straightforward, one-step epoxidation mechanism for compound A.•Evaluation of A, P1, and P2 includes molecular docking and dynamics to assess their potential as antidiabetic agents via alpha-amylase and alpha-glucosidase inhibition. Epoxidation of a β-himachalene derivative (A) can be carried out using meta-chloroperoxybenzoic acid (m-CPBA). An oxygen atom is added to the double bond C9C10, during the process, producing the epoxides P1 and P2. DFT calculations at the B3LYP/6-31G(d) level were used to study, Theoretically, the mechanism and stereoselectivity of the epoxidation reaction of compound A with m-CPBA. The calculation of activation energies associated with both possible reaction pathways, indicated that this epoxidation reaction is exothermic and highly stereoselective, favoring the formation of product P1 which is in agreement with the experimental results. Additionally, the IRC calculation shows that this reaction occurs via a one-step mechanism. The products P1, P2, and the starting compound A were evaluated for their antidiabetic activity and their potential to inhibit alpha-amylase and alpha-glucosidase through molecular docking, molecular dynamics, and ADMET studies. The evaluation of these three compounds aimed to study the effect of epoxidation and stereoselectivity on their inhibitory activity against the two enzymes.