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.
Bioorganic & medicinal chemistry letters. 2016 May 07 [Epub ahead of print]
Ying An, Eun Lee, Yeongji Yu, Jieun Yun, Myeong Youl Lee, Jong Soon Kang, Woo-Young Kim, Raok Jeon
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., 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., 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., Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea., Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea., Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea., 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., 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: .