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

[ Vol. 13 , Issue. 2 ]

Author(s):

Ade Arsianti*, Fadilah Fadilah, Kusmardi Kusmardi, Gede Y. Sugiarta, Hiroki Tanimoto and Kiyomi Kakiuchi   Pages 129 - 136 ( 8 )

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.

Keywords:

Synthesis, in silico, cytotoxicity, opened-chain analogue, antimycin A3, HEP-2, laryngeal cancer.

Affiliation:

Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Department of Medical Chemistry, Faculty of Medicine, Universitas Indonesia, Jakarta, Department of Anatomical pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Medical student of Faculty of Medicine, Universitas Indonesia, Jakarta, Synthetic Organic Chemistry Laboratory, Graduate School of Materials Science, Nara Institute of Science and Technology, Nara, Synthetic Organic Chemistry Laboratory, Graduate School of Materials Science, Nara Institute of Science and Technology, Nara

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