DESIGN, SYNTHESIS, AND CYTOTOXICITY EVALUATION OF NOVEL OPEN-CHAIN ANALOGUES OF ANTIMYCIN A 3 AS POTENTIAL ANTI-COLORECTAL CANCER AGENTS

Abstract

Objective: Colorectal cancer is the third most common diagnosed cancer in the world. The aim of this work was to design, to synthesize, and to
evaluate the novel open-chain analogues of antimycin A
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as highly potent anti-colorectal cancer agents.
Methods: Our analogue synthesis was designed by modifying the nine-membered dilactone moiety of antimycin A
with a simple open-chain
moiety, as well as introducing the stereocenter, and the hydroxyl groups on the side chain of the ester group. The synthesis was conducted through a
sequence of reactions from Boc-L-threonine by esterification, amidation, and sharpless asymmetric dihydroxylation. After completion the synthesis,
cytotoxicities of the analogues were evaluated as inhibitors of colorectal HCT-116 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide cell proliferation assay.
Results: Novel open-chain analogues of antimycin A
were successfully synthesized in a good yield. The analogues exhibited a greater anticancer
activity against colorectal HCT-116 cells than the original antimycin A
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with 50% inhibitory concentrations ranging of 35.0-47.0 µM. The results
indicated that the presence of stereocenter and a hydroxylated open-chain moiety in the analogues were successfully improved its anti-colorectal
cancer activity.
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Conclusion: Our results clearly demonstrate that the opened-chain analogues of antimycin A
as a promising candidates of new anti-colorectal cancer
agents.
Keywords: Design, Synthesis, Open-chain, Analogue, Antimycin A
, Anti-colorectal cancer.
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