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


Ade Arsianti, Fadilah Fadilah, Kusmardi Suid, Hiroki Tanimoto, Kiyomi Kakiuchi

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
3
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
3
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.
3
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.
3
3


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About this article

Title

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

Date

01-11-2015

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Vol 8 Issue 6 (November - December) 2015 Page: 120-124

Print ISSN

0974-2441

Online ISSN

2455-3891

Statistics

141 Views | 316 Downloads

Authors & Affiliations

Ade Arsianti
Faculty of Medicine, University of Indonesia
Indonesia

Fadilah Fadilah
Department of Medical Chemistry, Faculty of Medicine University of Indonesia
Indonesia

Kusmardi Suid
Department of Anatomical Pathology, faculty of Medicine, University of Indonesia
Indonesia

Hiroki Tanimoto
Graduate School of Materials Science, Nara Institute of Science and Technolgy (NAIST), Japan
Japan

Kiyomi Kakiuchi
Graduate School of Materials Science, Nara Institute of Science and Technolgy (NAIST), Japan


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