2. Academic Validation
  3. Synthesis, cytotoxicity, DNA binding and topoisomerase II inhibition of cassiarin A derivatives

Synthesis, cytotoxicity, DNA binding and topoisomerase II inhibition of cassiarin A derivatives

  • Bioorg Med Chem Lett. 2014 Jul 1;24(13):2845-50. doi: 10.1016/j.bmcl.2014.04.107.
Urarika Luesakul 1,  Tanapat Palaga 2,  Kuakarun Krusong 3,  Nattaya Ngamrojanavanich 1,  Tirayut Vilaivan 1,  Songchan Puthong 4,  Nongnuj Muangsin 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • 2 Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • 3 Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
  • 4 Antibody Production Research Unit, Institute of Biotechnology and Genetic Engineering, Chulalongkorn University, Bangkok 10330, Thailand.
  • 5 Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: nongnuj.j@chula.ac.th.
PMID: 24835201 DOI: 10.1016/j.bmcl.2014.04.107
Abstract

Four series of cassiarin A derivatives with alkanoyl (3a-3d), aroyl (4a-4d), hydroxy/amino-substituted ethylene glycol (5a-5c) and selenium-containing (6a) side chains were synthesized. Their antitumor activities were evaluated against BT474, CHAGO, HepG2, KATO-III, SW620 and CaSki Cancer cell lines. Preliminary results demonstrated that 5b had moderate activities against HepG2 and KATO-III cell lines, while 5c showed moderate to high cytotoxicity against most tested cell lines. In addition, 6a exhibited moderate cytotoxicity against cervical cells, CaSki. DNA-binding and ethidium bromide displacement experiments suggested that 5c and 5b binds to DNA via an intercalative mode, whereas 6a did not. However, the selenium-containing cassiarin A derivative 6a inhibited Topoisomerase II with more than 95% inhibition at the concentration of 50 μM. These cassiarin A derivatives showed lower toxicity to normal cells, WI-38 than amonafide therefore they are potential lead compounds to be further developed as new Anticancer agents.

Keywords

Amonafide; Cassiaria A; DNA-binding; Selenium compound; Topoisomerase II.

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