Synthesis of xanthone derivatives and studies on the inhibition against cancer cells growth and synergistic combinations of them

Eur J Med Chem. 2017 Jun 16:133:50-61. doi: 10.1016/j.ejmech.2017.03.068.

Jie Liu ¹, Jianrun Zhang ¹, Huailing Wang ², Zhijun Liu ¹, Cao Zhang ¹, Zhenlei Jiang ¹, Heru Chen ³

Affiliations

1 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China.
2 School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
3 Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, PR China; Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, PR China. Electronic address: thrchen@jnu.edu.cn.

PMID: 28376372 DOI: 10.1016/j.ejmech.2017.03.068

Abstract

34 Xanthones were synthesized by microwave assisted technique. Their in vitro inhibition activities against five cell lines growth were evaluated. The SAR has been thoroughly discussed. 7-Bromo-1,3-dihydroxy-9H-xanthen-9-one (3-1) was confirmed as the most active agent against MDA-MB-231 cell line growth with an IC₅₀ of 0.46 ± 0.03 μM. Combination of 3-1 and 5,6-dimethylxanthone-4-acetic acid (DMXAA) showed the best synergistic effect. Apoptosis analysis indicated different contributions of early/late Apoptosis and necrosis to cell death for both monomers and the combination. Western Blot implied that the combination regulated p53/MDM2 to a better healthy state. Furthermore, 3-1 and DMXAA arrested more cells on G2/M phase; while the combination arrested more cells on S phase. All the evidences support that the 3-1/DMXAA combination is a better anti-cancer therapy.

Keywords

Anti-cancer; Drug combination; Synergistic effect; Xanthones; p53-MDM2.

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