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Abstract
Invasive fungal infections including Candidiasis and Aspergillosis are associated with considerable morbidity and mortality in immunocompromised individuals, such as cancer patients. Aurora B is a key mitotic kinase required for the cell division of eukaryotes from fungus to man. Here, we identified a novel Aurora B inhibitor GSK650394 that can inhibit the recombinant Aurora B from human and Aspergillus fumigatus, with IC50 values of 5.68 and 1.29 µM, respectively. In HeLa and HepG2 cells, GSK650394 diminishes the endogenous Aurora B activity and causes cell cycle arrest in G2/M phase. Further cell-based assays demonstrate that GSK650394 efficiently suppresses the proliferation of both cancer cells and Aspergillus fumigatus. Finally, the molecular docking calculation and site-directed mutagenesis analyses reveal the molecular mechanism of Aurora B inhibition by GSK650394. Our work is expected to provide new insight into the combinational therapy of cancer and Aspergillus fumigatus infection.
Acknowledgements
We thank Dr. Shihua Wang, Dr. Yu Wang and Lijuan Yan at Fujian Agriculture and Forestry University (Fuzhou, China) for their assistances with the anti-Aspergillus fumigatus experiments.
Author contributions
Zhonghui Lin designed and supervised the project. Yuhua He performed biochemical and cell biological experiments. Liyang Du performed immunoblotting and flow cytometry analyses on the HepG2 cells. Zhengkang Hua provided assistance with protein expression and purification. Wei Fu conducted Molecular docking calculation under the supervision of Jinyu Li. Zhonghui Lin wrote the manuscript with input of all authors. All authors analysed the data and approved the final manuscript.
Disclosure statement
No potential conflict of interest was reported by the author(s).