2. Academic Validation
  3. Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents

Synthesis and biological evaluation of benzimidazole acridine derivatives as potential DNA-binding and apoptosis-inducing agents

  • Bioorg Med Chem. 2015 Apr 15;23(8):1800-7. doi: 10.1016/j.bmc.2015.02.036.
Chunmei Gao 1,  Bin Li 2,  Bin Zhang 2,  Qinsheng Sun 3,  Lulu Li 3,  Xi Li 2,  Changjun Chen 2,  Chunyan Tan 4,  Hongxia Liu 4,  Yuyang Jiang 5
Affiliations

Affiliations

  • 1 Tsinghua University, Department of Chemistry, Beijing 100084, PR China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, PR China; National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China. Electronic address: chunmeigao@sz.tsinghua.edu.cn.
  • 2 Tsinghua University, Department of Chemistry, Beijing 100084, PR China; The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, PR China.
  • 3 The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, PR China.
  • 4 The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, PR China; National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China.
  • 5 The Ministry-Province Jointly Constructed Base for State Key Lab-Shenzhen Key Laboratory of Chemical Biology, Shenzhen 518055, PR China; National & Local United Engineering Lab for Personalized Anti-tumor Drugs, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China; School of Medicine, Tsinghua University, Beijing 100084, PR China. Electronic address: jiangyy@sz.tsinghua.edu.cn.
PMID: 25778766 DOI: 10.1016/j.bmc.2015.02.036
Abstract

The discovery of new effective DNA-targeted antitumor agent is needed because of their clinical significance. As acridines can intercalate into DNA and benzimidazoles have the ability to bind in the DNA minor groove, a series of novel benzimidazole acridine derivatives were designed and synthesized to be new DNA-targeted compounds. MTT assay indicated that most of the synthesized compounds displayed good antiproliferative activity, among which compound 8l demonstrated the highest activity against both K562 and HepG-2 cells. Further experiments showed that 8l displayed good DNA-binding capability and inhibited Topoisomerase I activity. Moreover, compound 8l could induce Apoptosis in K562 cell lines through mitochondrial pathway. These data suggested that compound 8l might be potential as new DNA-binding and apoptosis-inducing antitumor agents.

Keywords

Acridine; Antitumor; Benzimidazole; DNA; Topoisomerase I.

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