Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson’s Disease Effect

• Published in: International journal of molecular sciences Vol. 24; no. 22; p. 16196
• Main Authors: Cai, Min, Bai, Xiao-Lin, Zang, Hao-Jing, Tang, Xiao-Han, Yan, Ying, Wan, Jia-Jia, Peng, Min-You, Liang, Hong, Liu, Lin, Guo, Feng, Zhao, Pei-Ji, Liao, Xun, Di, Ying-Tong, Hao, Xiao-Jiang
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.11.2023
• Subjects: Harrisonia perforata; Hydrogenation; Kinases; Natural products; neuroprotection; Parkinson's disease; PC12 cells; PINK1B9 flies; quassinoid; simarubaceae
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms242216196

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1–7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer–Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson’s disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson’s disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10–15% increase in cell viability of the model cells at 50 μM, while compounds 2 and 4 (100 μM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.