2. Academic Validation
  3. Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents

Design, synthesis and biological evaluation of matrine derivatives as potential anticancer agents

  • Bioorg Med Chem Lett. 2018 Feb 15;28(4):677-683. doi: 10.1016/j.bmcl.2018.01.017.
Zheng Li 1,  Mengyang Luo 1,  Bin Cai 2,  Lichuan Wu 3,  Mengtian Huang 1,  Haroon-Ur-Rashid 1,  Jun Jiang 4,  Lisheng Wang 5
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China.
  • 2 Suzhou Galaxy biopharma, CO., LTD., Suzhou, Jiangsu 215000, PR China.
  • 3 Medical College of Guangxi University, Guangxi 530004, PR China.
  • 4 School of Chemistry and Chemical Engineering, Guangxi University, Nanning, Guangxi 530004, PR China. Electronic address: jiangjun@gxu.edu.cn.
  • 5 Medical College of Guangxi University, Guangxi 530004, PR China. Electronic address: lswang@gxu.edu.cn.
PMID: 29395978 DOI: 10.1016/j.bmcl.2018.01.017
Abstract

Using matrine (1) as the lead compound, a series of new 14-(N-substituted-2-pyrrolemethylene) matrine and 14-(N-substituted-indolemethylene) matrine derivatives was designed and synthesized for their potential application as Anticancer agents. The structure of these compounds was characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against three human Cancer cell lines (SMMC-7721, A549 and CNE2). The results revealed that compound A6 and B21 displayed the most significant Anticancer activity against three Cancer cell lines with IC50 values in range of 3.42-8.05 μM, which showed better activity than the parent compound (Matrine) and positive control Cisplatin. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound A6 and B21 could significantly induce the Apoptosis of SMMC-7721 and CNE2 cells in a dose-dependent manner. The cell cycle analysis also revealed that compound A6 could cause cell cycle arrest of SMMC-7721 and CNE2 cells at G2/M phase.

Keywords

Anticancer; Apoptosis; Cell cycle arrest; Derivatives; Indole; Matrine; Pyrrole; Structure-activity relationship.

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