2. Academic Validation
  3. Synthesis and biological evaluation of 4β-(thiazol-2-yl)amino-4'-O-demethyl-4-deoxypodophyllotoxins as topoisomerase-II inhibitors

Synthesis and biological evaluation of 4β-(thiazol-2-yl)amino-4'-O-demethyl-4-deoxypodophyllotoxins as topoisomerase-II inhibitors

  • Bioorg Med Chem Lett. 2018 Jan 15;28(2):71-76. doi: 10.1016/j.bmcl.2017.12.012.
Chun-Yan Sang 1,  Heng-Zhi Tian 1,  Yue Chen 2,  Jian-Fei Liu 1,  Shi-Wu Chen 3,  Ling Hui 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 2 College of Life Science, Northwest Normal University, Lanzhou 730070, China.
  • 3 School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: chenshw@lzu.edu.cn.
  • 4 Experimental Center of Medicine, General Hospital of Lanzhou Military Command, Lanzhou 730050, China; Key Laboratory of Stem Cells and Gene Drug of Gansu Province, General Hospital of Lanzhou Military Command, Lanzhou 730050, China. Electronic address: zyhuil@hotmail.com.
PMID: 29248296 DOI: 10.1016/j.bmcl.2017.12.012
Abstract

A series of 4β-(thiazol-2-yl)amino-4'-O-demethyl-4-deoxypodophyllotoxins were synthesized, and their cytotoxicities were evaluated against four human Cancer cell lines (A549, HepG2, HeLa, and LOVO cells) and normal human diploid fibroblast line WI-38. Some of the compounds exhibited promising antitumor activity and less toxicity than the Anticancer drug etoposide. Among them, compounds 15 and 17 were found to be the most potent synthetic derivatives as topo-II inhibitors, and induced DNA double-strand breaks via the p73/ATM pathway as well as the H2AX phosphorylation in A549 cells. These compounds also arrested A549 cells cycle in G2/M phase by regulating cyclinB1/cdc2(p34). Taken together, these results show that a series of compounds are potential Anticancer agents.

Keywords

Cell cycle arrest; DSBs; Podophyllotoxin; Topo-II inhibitors.

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