Novel rotundic acid derivatives: Synthesis, structural characterization and in vitro antitumor activity

Chen,Yu; He,Yu-Fang; Nan,Min-Lun; Sun,Wen-Yi; Hu,Jie; Cui,Ai; Li,Fan; Wang,Fang

doi:10.3892/ijmm.2012.1206

Novel rotundic acid derivatives: Synthesis, structural characterization and in vitro antitumor activity

Authors:
- Yu Chen
- Yu-Fang He
- Min-Lun Nan
- Wen-Yi Sun
- Jie Hu
- Ai Cui
- Fan Li
- Fang Wang
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Affiliations: Department of Pathogenobiology, Norman Bethune College of Medicine, Jilin University, Changchun, Jilin 130021, P.R. China, Jilin Academy of Chinese Medicine Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: December 6, 2012 https://doi.org/10.3892/ijmm.2012.1206
Pages: 353-360

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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, 1H NMR and 13C NMR. The derivatives were evaluated for cytotoxic properties on the following three tumor cell lines: HeLa, HepG2 and SGC-7901. Compound 4f showed better cytotoxic activity compared with RA treatment and lower IC50 (4.16 µM) on HepG2 cells than on HeLa (8.54 µM) and SGC-7901 cells (11.32 µM). The anticancer mechanism of compound 4f was studied through cell cycle progression and apoptosis. Notably, compound 4f was able to induce apoptosis and G0/G1 cell cycle arrest of HepG2 at a concentration of 4.16 µM. In summary, RA was modified to obtain six novel derivatives. Compound 4f exhibited better cytotoxicity and may be developed as a potential agent against hepatocellular carcinoma.

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