2. Academic Validation
  3. Novel conjugates of podophyllotoxin and coumarin: Synthesis, cytotoxicities, cell cycle arrest, binding CT DNA and inhibition of Topo IIβ

Novel conjugates of podophyllotoxin and coumarin: Synthesis, cytotoxicities, cell cycle arrest, binding CT DNA and inhibition of Topo IIβ

  • Bioorg Med Chem Lett. 2019 Aug 15;29(16):2129-2135. doi: 10.1016/j.bmcl.2019.06.063.
Shu-Yi Hao 1,  Shi-Liang Feng 1,  Xing-Rong Wang 1,  Zhichao Wang 2,  Shi-Wu Chen 3,  Ling Hui 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
  • 2 College of Chemical Engineering, Northwest Minzu University, Lanzhou 730000, China.
  • 3 School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address: chenshw@lzu.edu.cn.
  • 4 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: 31278032 DOI: 10.1016/j.bmcl.2019.06.063
Abstract

A series of conjugates of podophyllotoxin and coumarin were prepared using the click reaction, and their cytotoxicities against A549, HepG2, HeLa, and LoVo cells were evaluated. Among them, compound 14e exhibited the strongest cytotoxicities against these Cancer cells with IC50 values of 4.9-17.5 μM. Furthermore, 14e disrupted microtubules and induced cell cycle arrest at G1 phase by regulating P21 and Cyclin D1 in LoVo cells. In addition, 14e bond CT DNA and selectively inhibited Topo IIβ over Topo IIα. Molecular docking model showed that 14e appeared to form stable hydrogen bonds with several DNA Bases and residue Gln778. Taken together, these conjugates have the potential to be developed as anti-tumor drugs.

Keywords

Cell cycle arrest; Conjugates; Coumarin; Podophyllotoxin; Topo Ⅱ.

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