AI Article Synopsis
- The Aurora kinases, important in cell division, are being explored as drug targets for cancer treatment.
- Researchers synthesized 15 new compounds, finding that compound 11c was particularly effective, showing significant cytotoxicity against tumor cells and a strong preference for inhibiting Aurora A over Aurora B.
- Compound 11c induced cell cycle arrest in cancer cells, suggesting it could be developed further as a selective inhibitor for targeting cancer growth.
Article Abstract
The Aurora kinases are a family of serine/threonine kinases that interact with components of the mitotic apparatus and serve as potential therapeutic targets in oncology. Here we synthesized 15 2,4-diaminopyrimidines and evaluated their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects. These compounds generally exhibited more potent cytotoxicity against tumor cell lines compared with the VX-680 control, especially compound 11c, which showed the highest cytotoxicities, with IC50 values of 0.5-4.0 μM. Compound 11c had more than 35-fold more selectivity for Aurora A over Aurora B, and molecular docking analysis indicated that compound 11c form better interaction with Aurora A both from the perspective of structure and energy. Furthermore, compound 11c induced G2/M cell cycle arrest in HeLa cells. This series of compounds has the potential for further development as selective Aurora A inhibitors for anticancer activity.
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| http://dx.doi.org/10.1016/j.ejmech.2015.03.044 | DOI Listing |
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