Rotundic acid (RA, 1), a natural compound, exhibits potent tumor cell growth inhibiting properties. To date there are no reports on derivatives of RA. Furthermore, the 28-COOH position of RA might make it unstable and induced serious gastrointestinal side effects when it was applied in vivo. Therefore, in order to explore and make use of this compound, eight new amino acid derivatives of RA at the 28-COOH position were synthesized and evaluated for their cytotoxicities in vitro on three tumor cell lines including A375, HepG2 and NCI-H446. As a result, a few of these new amino acid derivatives showed stronger cytotoxicity. Compound 5a was found to have the best inhibition activity on the three tested human tumor cell lines with IC50 values of less than 10 μM compared with RA treatment. Meanwhile, the cytotoxicity of compound 6b was significantly higher than that of RA on the A375 cell line and almost the same as RA on the HepG2 and NCI-H446 cell lines. Hence, compounds 5a and 6b may serve as potential lead compounds for the development of new anti-tumor drugs.
In light of the important antitumor activity of acylhydrazone compounds and based on our previous study, 18 new rotundic acid (RA) acylhydrazone derivatives were synthesized. All of the compounds were characterized by their spectroscopic data. The antiproliferative activity of the compounds was evaluated in vitro via the MTT method in three tumor cell lines, including A-375 (human malignant melanoma cells), SPC-A1 (human lung adenocarcinoma) and NCI-H446 (small cell lung cancer). The results showed that the antiproliferative activity of all of the compounds on the NCI-H446 cell line did not increase compared to RA, however, most of the derivatives exhibited higher activity against the A375 and SPC-A1 cell lines as compared to RA. Importantly, the antiproliferative activities of compounds 5a and 5b were the highest among the compounds, with IC(50) values <10 μM. Collectively, compounds 5a and 5b may act as potential anti-tumor agents in the future.
Abstract. Six novel rotundic acid (RA, 1) derivatives 4a-4f modified at the 28-COOH position were synthesized, and their structures were confirmed by IR, MS,
Rotundic acid (RA) is a kind of pentacyclic triterpene saponins, which widely exists in holly and other plants. It has anti-tumor and lipid-lowering effects, and has been widely used in the prevention and treatment of vascular diseases. Succinyl RA (SRA) is a kind of circular acid derivative
with strong water solubility. However, SRA’s effect and mechanism about the therapy of cervical cancer is still not clarified. The inhibitory effect of SRA on Hela cells and its molecular mechanism were investigated in this study. Hela cell line was used to establish an in vitro
model to study the effect of SRA. The effects of SRA on cell proliferation, cell cycle and apoptosis were analyzed by flow cytometry and detected by 3-(4,5-dimethyl thiazole-2-yl)-2, 5-diphenyltetrazole bromide. The experimental results show that SRA can inhibit the growth of Hela and diffusion,
inducing cell apoptosis. SRA can also reduce the expression of CyclinD 1 and p21. It was also decreased the expression of apoptosis inhibitor B cell lymphoma (Bcl-2), and increased the expression of Bcl-2-related X-protein and Caspase-3. This study provides evidence for
the progress of SRA in inhibiting Hela cells and presents potential applications of SRA as an alternative therapy for cervical cancer.
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