Identification of nitroimidazole-oxime derivatives targeting the polo-box domain of polo-like kinase 1

Publication date: Available online 28 October 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Juan Sun, Han-Yu Liu, Ruo-Fei Xu, Hai-Liang Zhu
Recent progress in the development of small molecular skeleton-derived Polo-like kinase (PLK1) catalytic domain (KD) inhibitors has led to the synthesis of multiple ligands with high binding affinity. However, few systematic analyses have been conducted to identify key PLK1-PBD domain and characterize their interactions with potent PLK1 inhibitors. Therefore, we designed a series of PLK1-PBD inhibitors with an in silico scaffold modification strategy. A docking simulation combined with a primary screen in vitro were performed to filter for the lead compound, which was then substituted, synthesized and evaluated by a variety of bioassays. The biological profile of 4v suggests that this compound may be developed as a potential anticancer agent.

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