1. Four undescribed coumarin derivatives, with ten amides from the roots of Ficus hirta and their cytotoxic activities.
- Author
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Ye, Xian-Sheng, Tian, Wen-Jing, Wang, Guang-Hui, Hu, Li-Juan, Leng, Chang-Long, Sun, Bin-Lian, Liu, Wei, Shu, Xi-Ji, and Chen, Hai-Feng
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COUMARIN derivatives , *AMIDES , *COUMARINS , *HELA cells , *BAX protein , *CERVICAL cancer - Abstract
[Display omitted] • Four undescribed coumarins derivatives, including ficusalt A (1) and ficusalt B (2), and a pair of racemic coumarins, (±) ficudimer A (3a / 3b), were isolated from the roots of Ficus hirta. • Compound 5 had distinct cytotoxic activity against HeLa cells, induced their apoptosis, and significantly inhibited their invasion and migration. • Compound 5 obviously increased the cleavage of PARP, the phosphorylation level of p38 and JNK, and the expression of pro-apoptotic protein of Bax, whereas inhibited the expression of p-ERK and p-AKT. Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a / 3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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