Design, Synthesis, and Biochemical Evaluation of New Triazole Derivatives as Aurora-A Kinase Inhibitors

Molecules. 2021 Sep 18;26(18):5678. doi: 10.3390/molecules26185678.

Abstract

Aurora-A kinase, a key mitosis regulator, is expressed in a cell cycle-dependent manner and has an essential role in maintaining chromosomal stability and the normal progression of the cell through mitosis. Aurora-A kinase is overexpressed in many malignant solid tumors, such as breast, ovarian, colon, and pancreatic cancers. Thus, inhibiting Aurora-A kinase activity is a promising approach for cancer treatment. Here, new triazole derivatives were designed as bioisosteric analogues of the known inhibitor JNJ-7706621. The new compounds showed interesting inhibitory activity against Aurora-A kinase, as attested by IC50s in the low to submicromolar range.

Keywords: Aurora-A; cancer; kinase; triazole.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Aurora Kinase A*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • HeLa Cells
  • Humans
  • Mitosis / drug effects
  • Protein Kinase Inhibitors*
  • Triazoles*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Triazoles
  • Aurora Kinase A