2. Academic Validation
  3. One-pot synthesis and biological evaluation of N-(aminosulfonyl)-4-podophyllotoxin carbamates as potential anticancer agents

One-pot synthesis and biological evaluation of N-(aminosulfonyl)-4-podophyllotoxin carbamates as potential anticancer agents

  • Bioorg Med Chem Lett. 2017 Jul 1;27(13):2890-2894. doi: 10.1016/j.bmcl.2017.04.082.
Xiao-Hui Xu 1,  Xiao-Wen Guan 2,  Shi-Liang Feng 2,  You-Zhen Ma 2,  Shi-Wu Chen 3,  Ling Hui 4
Affiliations

Affiliations

  • 1 School of Pharmacy, Lanzhou University, Lanzhou 730000, China; Lanzhou Institutes for Food and Drug Control, Gansu Province, Lanzhou 730000, China.
  • 2 School of Pharmacy, Lanzhou University, Lanzhou 730000, 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: 28512026 DOI: 10.1016/j.bmcl.2017.04.082
Abstract

A series of N-(aminosulfonyl)-4-podophyllotoxin carbamates were synthesized via the Burgess-type intermediate, and their antiproliferative activities were evaluated. Most of them possessed more potent cytotoxic effects against four human tumor cell lines (HeLa, A-549, HCT-8 and HepG2) and less toxic to normal human fetal lung fibroblast WI-38 cells than etoposide. In particular, N-(morpholinosulfonyl)-4-podophyllotoxin carbamate (9) exhibited the most potent activity towards these four tumor cells with IC50 values in the range of 0.5-16.5μM. Furthermore, immunofluorescence analysis revealed that 9 induced cell Apoptosis by up-regulating the expression of p53 and ROS. Meanwhile, 9 effectively inhibited tubulin polymerization and microtubule assembly at cellular levels in HeLa cells. In addition, 9 could induce cell cycle arrest in the G2/M phase in HeLa cells by up-regulating levels of cyclinB1 and cdc2 and decreasing the expression of p-cdc2. These results indicated that 9 had potential for further development as Anticancer agents.

Keywords

Apoptosis; Cell cycle arrest; Microtubule assembly; Podophyllotoxin; Tubulin polymerization.

Figures