title: Design and synthesis of novel benzoxazole analogs as Aurora B kinase inhibitors.
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.
authors.affiliation: 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.
authors.forename: Ying
authors.initials: Y
authors.lastname: An
authors.affiliation: 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.
authors.forename: Eun
authors.initials: E
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Yeongji
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.affiliation: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea.
authors.forename: Myeong Youl
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungcheongbuk-do 28116, Republic of Korea.
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: 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.
authors.forename: Woo-Young
authors.initials: WY
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D001583:Benzoxazoles; D047428:Protein Kinase Inhibitors; C576921:AURKB protein, human; D064107:Aurora Kinase B
keywords: Antiproliferation; Aurora B kinase; Benzoxazole analogs