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Updated: Mar 2, 2026
Real-Time Monitoring of Aurora kinase A Activation using Conformational FRET Biosensors in Live Cells
Published on: July 30, 2020
Optimization and biological evaluation of 2-aminobenzothiazole derivatives as Aurora B kinase inhibitors
Eun Lee1, Ying An1, Junhee Kwon2
1Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Cheongpa-ro 47-gil 100, Yongsan-gu, Seoul 04310, Republic of Korea.
Abstract:
A strong relationship between abnormal functions of Aurora kinases and tumorigenesis has been reported for decades. Consequently, Aurora kinases serve as potential targets for anticancer agents. Here, we identified aminobenzothiazole derivatives as novel inhibitors of Aurora B kinase through bioisosteric replacement of the previous inhibitors, aminobenzoxazole derivatives. Most of the urea-linked aminobenzothiazole derivatives showed potent and selective inhibitory activity against Aurora B kinase over Aurora A kinase. Molecular modeling indicated that compound 15g bound well to the active site of Aurora B kinase and formed the essential hydrogen bonds. The potent compounds, 15g and 15k, were selected, and their biological effects were evaluated using HeLa cell lines. It was found that these compounds inhibited the phosphorylation of histone H3 at Ser10 and induced G2/M cell cycle arrest. We suggest that the reported compounds have the potential to be further developed as anticancer therapeutics.
Insights
Novel aminobenzothiazole derivatives show potent anticancer activity by inhibiting Aurora B kinase, a key target in tumorigenesis. These compounds effectively arrest cancer cell growth at the G2/M phase, offering potential for new cancer therapeutics.
Area of Science:
- Medicinal Chemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Abnormal Aurora kinase function is linked to tumorigenesis, making these enzymes potential anticancer drug targets.
- Previous research focused on aminobenzoxazole derivatives as kinase inhibitors.
Purpose of the Study:
- To identify novel inhibitors of Aurora B kinase using aminobenzothiazole derivatives.
- To evaluate the anticancer potential of these new compounds.
Main Methods:
- Bioisosteric replacement of aminobenzoxazoles with aminobenzothiazoles.
- Synthesis and screening of urea-linked aminobenzothiazole derivatives.
- Molecular modeling to assess binding affinity to Aurora B kinase.
- In vitro evaluation using HeLa cell lines to assess biological effects.
Main Results:
- Several urea-linked aminobenzothiazole derivatives demonstrated potent and selective inhibition of Aurora B kinase over Aurora A.
- Compound 15g showed favorable binding to the Aurora B kinase active site.
- Compounds 15g and 15k inhibited histone H3 phosphorylation and induced G2/M cell cycle arrest in HeLa cells.
Conclusions:
- Aminobenzothiazole derivatives represent a promising class of novel Aurora B kinase inhibitors.
- These compounds exhibit anticancer activity by disrupting cell cycle progression.
- Further development of these compounds as anticancer therapeutics is warranted.
