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Bioorg Med Chem Lett. 2016 Jul 1;26(13):3067-3072. doi: 10.1016/j.bmcl.2016.05.017. Epub 2016 May 7.

Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors.

Author information

1
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul 04310, Republic of Korea.
2
Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea.
3
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul 04310, Republic of Korea. Electronic address: rjeon@sookmyung.ac.kr.

Abstract

A novel series of benzoxazole analogs was designed and synthesized, and their inhibitory activities against Aurora kinases were evaluated. Some of the tested compounds exhibited a promising activity with respect to the inhibition of Aurora B kinase. A structure-activity relationship study indicated that linker length, regiochemistry, and halogen substitution play important roles in kinase inhibitory potency. The binding modes between representative compounds and Aurora kinases were interpreted through a molecular docking study to explain the inhibitory activity and selectivity for Aurora A and B kinases. Compounds 13l and 13q also show an antiproliferative effect on the human tumor cell lines in a dose-dependent manner. The most potent 13q demonstrated good efficacy in the prostate cancer PC-3 tumor xenograft model.

KEYWORDS:

Antiproliferation; Aurora B kinase; Benzoxazole analogs

PMID:
27209235
DOI:
10.1016/j.bmcl.2016.05.017
[Indexed for MEDLINE]

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