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
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.