Synthesis and biological evaluation of 2,4-disubstituted phthalazinones as Aurora kinase inhibitors

Wei Wang, Xiu Feng, Huan Xiang Liu, Shi Wu Chen, Ling Hui

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17 Citations (Scopus)


A series of 2,4-disubstituted phthalazinones were synthesized and their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects were evaluated. Among them, N-cyclohexyl-4-((4-(1-methyl-1H-pyrazol-4-yl)-1-oxophthalazin-2(1H)-yl) methyl) benzamide (12c) exhibited the most potent antiproliferation against five carcinoma cell lines (HeLa, A549, HepG2, LoVo and HCT116 cells) with IC50 values in range of 2.2–4.6 μM, while the IC50 value of reference compound VX-680 was 8.5–15.3 μM. Moreover, Aurora kinase assays exhibited that compound 12c was potent inhibitor of AurA and AurB kinase with the IC50 values were 118 ± 8.1 and 80 ± 4.2 nM, respectively. Molecular docking studies indicated that compound 12c forms better interaction with both AurA and AurB. Furthermore, compound 12c induced G2/M cell cycle arrest in HeLa cells by regulating protein levels of cyclinB1 and cdc2. These results suggested that 12c is a promising pan-Aurora kinase inhibitor for the potential treatment of cancer.

Original languageEnglish
Pages (from-to)3217-3226
Number of pages10
JournalBioorganic and Medicinal Chemistry
Issue number12
Publication statusPublished - 23 Jul 2018
Externally publishedYes


  • Antitumor
  • Aurora kinase
  • Cell cycle
  • Phthalazinone


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