title: Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole-benzimidazole derivatives as potent Aurora A/B kinase inhibitors.
abstract: Novel pyrazole-benzimidazole derivatives have been designed and synthesized. The entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro. The compounds 7a, 7b, 7i, 7k and 7l demonstrated significant cancer cell lines and Aurora A/B kinase inhibitory activities. Molecular modeling studies suggested the derivatives have bound in the active site of Aurora A kinase through the formation of four hydrogen bonds. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. The cellular activity of 7k was also tested by immunofluorescence.
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou 221004, China.
authors.forename: Youguang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Ming
authors.initials: M
authors.lastname: Zheng
authors.forename: Xin
authors.initials: X
authors.lastname: Ling
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Xue
authors.forename: Lin
authors.initials: L
authors.lastname: An
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.forename: Min
authors.initials: M
authors.lastname: Ji
authors.forename: Min
authors.initials: M
authors.lastname: Jin
mesh_terms: D064096:Aurora Kinase A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000737:chemistry; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; C576917:AURKA protein, human; C576921:AURKB protein, human; D064096:Aurora Kinase A; D064107:Aurora Kinase B