In Silico Study and Cytotoxicity of the Synthesized Open-chain Analogues of Antimycin A3 Against HEP-2 Laryngeal Cancer Cells

摘要

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 laryngealcancer. 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 anticanceractivity 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.