In silico study and cytotoxicity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells

Ade Arsianti, Fadilah, Kusmardi, Gede Y. Sugiarta, Hiroki Tanimoto, Kiyomi Kakiuchi

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Laryngeal cancers affect one quarter of all head and neck cancers. Chemotherapy is a standard method in treatment laryngeal carcinoma. However, cancer chemotherapy is often a failure due to the appearance of drug resistance. This fact suggests that the search for novel, safe, and more effective laryngeal cancer drugs are required. Antimycin A3 is a fit ligand of anti-apoptotic Bcl-2. While Bcl-2 is known to be over-expressed in laryngeal cancer cell, it is quite reasonable to expect antimycin A3 and its analogue to induce apoptosis in those cells. Methods: With this viewpoint, we decided to conduct research that is aimed to evaluate cytotoxic activity of the synthesized open-chain analogues of antimycin A3 against HEP-2 laryngeal cancer cells, as well as to conduct in silico study of the analogues on receptor binding target Bcl-2 of laryngeal cancer. Results and Conclusion: Open-chain analogues of antimycin A3 were successfully synthesized in a good yield from Boc-L-Threonine by esterification, amidation, and Sharpless asymmetric dihydroxylation. Consistent with in silico study, the analogues exhibited a greater anticancer activity against laryngeal HEP-2 cells than the original antimycin A3 with IC50 ranging of 31.6 µM to 46.3 µM. Our results clearly demonstrate that the open-chain analogues of antimycin A3 as a promising candidates of new anti-laryngeal cancer agents.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalCurrent Cancer Therapy Reviews
Volume13
Issue number2
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • Antimycin A
  • Cytotoxicity
  • HEP-2
  • In silico
  • Laryngeal cancer
  • Opened-chain analogue
  • Synthesis

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