Antioxidative limonoids from Swietenia macrophylla fruits: Experimental, DFT (Density Functional Theory) approach, and docking study

• Published in: Journal of molecular structure 2023-07, Vol.1283, p.135264, Article 135264
• Main Authors: Thuy, Phan Thi, Hieu, Tran Trung, Duc, Dau Xuan, Van Trung, Hoang, Hung, Nguyen Huy, Setzer, William N., Thang, Tran Dinh, Son, Ninh The
• Format: Article
• Language: English
• Subjects: Antioxidant; Density functional theory; Limonoid; Molecular docking; Mosquito larvicidal; Swietenia macrophylla
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135264

•Limonoids are the main constituents of Swietenia macrophylla fruits.•Seneganolide is better than the positive control ascorbic acid in DPPH radical scavenging.•Experimental results were aided by density functional theory and docking calculations. Phytochemical investigation of the methanol extract of Swietenia macrophylla fruit first led to the isolation of four limonoids seneganolide (1), khayanone (2), khayanolide B (3), and 6-acetoxy-methyl angolensate (4). Compound 3 (IC50 3.18 µg/mL) was better than the positive control ascorbic acid (IC50 7.18 µg/mL) in an antioxidative assay against DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals. Compound 1 showed strong mosquito larvicidal activity against Aedes aegypti with LC50 values of 34.1–44.1 µg/mL and LC90 values of 57.3–65.1 µg/mL for 24 and 48-h exposures. Based on DFT (density functional theory)/B3LYP/6–311G(d,p) method, the SPL-ET (sequential proton loss-electron transfer) antioxidative mechanism is essential for compound 3 in polar solvents, while the HAT antioxidative route is appropriate in weak or non-polar mediums. Methine group at carbon C-6 of this compound exerted the lowest BDE (bond dissociation energy) values of 72.9–73.8 kcal/mol in both four studied mediums gas, benzene, methanol, and water. In the kinetic reactions with HOO•, CH3OO•, and •NO2 radicals, 6-CH also generated the lowest Gibbs free energy of activation ΔG# values of 14.5–24.2 kcal/mol and the highest rate constant K values of 6.068 × 101–1.75 × 106 L/mol.s. A molecular docking (MD) analysis of seneganolide with relevant Ae. aegypti protein targets revealed AChR (acetylcholine receptor), ACE2 (angiotensin converting enzyme 2), and aaNAT (arylalkylamine N-acetyltransferase) to be potential targets of this compound. [Display omitted]