College of Chemistry, Fuzhou University, Fuzhou, China.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):109-117. doi: 10.1080/14756366.2021.1975693.
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 , with IC 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 . 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 infection.
侵袭性真菌感染，包括念珠菌病和曲霉病，与免疫功能低下者（如癌症患者）的发病率和死亡率密切相关。极光激酶 B 是一种关键的有丝分裂激酶，对于从真菌到人等真核生物的细胞分裂是必需的。在这里，我们鉴定出一种新型的极光激酶 B 抑制剂 GSK650394，它可以抑制来自人和的重组极光激酶 B，IC 值分别为 5.68 和 1.29 μM。在 HeLa 和 HepG2 细胞中，GSK650394 可降低内源性极光激酶 B 的活性，并导致细胞周期在 G2/M 期停滞。进一步的细胞检测证实，GSK650394 可有效抑制癌细胞和的增殖。最后，分子对接计算和定点突变分析揭示了 GSK650394 抑制极光激酶 B 的分子机制。我们的工作有望为癌症和真菌感染的联合治疗提供新的思路。
