Structurally Diverse Limonoids from Trichilia connaroides and Their Antitumor Activities

• Published in: Chinese journal of chemistry 2024-12, Vol.42 (24), p.3567-3580
• Main Authors: Yan, Ying, Wang, Dan, Zhou, Fang‐Jiao, Zhao, Yu‐Han, Qin, Xu‐Jie, Zhang, Yu, Ding, Xiao, Hao, Xiao‐Jiang
• Format: Article
• Language: English
• Subjects: Antitumor activities; Apoptosis; Cancer treatment; Cell cycle; Cytotoxicity; Doxorubicin; Limonoids; Meliaceae; Natural products; Oxidation; p53 and p21; p53 Protein; Structure elucidation; Structure‐activity relationships; Toxicity testing; Trichilia; Trichilia connaroides; Tumor cell lines; X-ray diffraction
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202400923

Comprehensive Summary Twelve new limonoids (1—12), named trichilitins A—L, were isolated from the leaves and twigs of Trichilia connaroides, together with ten known compounds (13—22). The structures were elucidated by extensive spectroscopic investigations, X‐ray diffraction analyses, and ECD calculations. Compound 1, which belongs to a unique class of ring B‐seco limonoid, has been identified as 6/7/6/5 tetracyclic due to a key Baeyer‐Villiger oxidation. Compounds 2—7 were identified as ring intact limonoids, while compounds 8—10 were established as ring D‐seco ones, and 11 and 12 were determined to be rearranged ones. All of the compounds were tested for cytotoxicity against three human tumor cell lines (HCT‐116, NCl‐H1975, and SH‐SY5Y). Compounds 6, 7, 13, 14, and 19 exhibited significant cytotoxic effects, especially 7 exhibited significant cytotoxic effects against HCT‐116 with an IC50 value of 0.035 μmol·L–1 and was more active than the positive control, doxorubicin with an IC50 value of 0.20 μmol·L–1. Compound 7 effectively induced apoptosis of HCT‐116, which was associated with S‐phase cell cycle arrest. Furthermore, the Western blot analysis showed that compound 7 could induce cell cycle arrest by promoting the expression levels of p53 and p21. Twelve new limonoids, trichilitins A—L (1—12), together with ten reported congeners (13—22) were isolated from Trichilia connaroides. Compounds 6, 7, 13, 14, and 19 exhibited significant cytotoxic effects, especially 7 exhibited significant cytotoxic effects against HCT‐116 with an IC50 value of 0.035 μmol·L–1 and induced cell cycle arrest by promoting the expression levels of p53 and p21.