Structurally Diverse Limonoids from Trichilia connaroides and Their Antitumor Activities

Abstract

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 IC ₅₀ value of 0.035 µmol·L ^–1 and was more active than the positive control, doxorubicin with an IC ₅₀ 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.

Keywords

Natural products / Limonoids / Meliaceae / Structure elucidation / Trichilia connaroides / Antitumor activities / p53 and p21 / Structure-activity relationships / Cancer treatment

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