Bibliographic Details
| Title: |
Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro. |
| Authors: |
Pechlivani, Louisa, Ntemou, Nikoleta, Pantazi, Despoina, Alivertis, Dimitrios, Skobridis, Konstantinos, Tselepis, Alexandros D. |
| Source: |
Pharmaceuticals (14248247); Mar2024, Vol. 17 Issue 3, p349, 17p |
| Subject Terms: |
CANCER cell proliferation, BLOOD platelet aggregation, CHRONIC myeloid leukemia, NILOTINIB, PROTEIN-tyrosine kinase inhibitors, PROTEIN-tyrosine kinases |
| Abstract: |
Nilotinib, a second-generation tyrosine kinase inhibitor for the treatment of chronic myelogenous leukemia (CML), inhibits Bcr-Abl tyrosine kinase activity and proliferation of Bcr-Abl-expressing cells, as well as other malignancies. In the present study, new nilotinib analogues were synthesized and fully characterized. A platelet aggregation assay was performed, and the expression of P-selectin and PAC-1, as well as the effect on the proliferation of healthy endothelial cells, were evaluated. The expression and antimetastatic effects of E-cadherin and N-cadherin were assessed. The analogues inhibited platelet aggregation in a statistically significant manner compared to nilotinib, while they exhibited a strong inhibitory effect on P-selectin and PAC-1 expression when activated by AA. All three analogues caused arrest in the mitosis phase of the HepG2 cell cycle, while analogue-1 exhibited the most potent apoptotic effect compared to nilotinib. Interestingly, none of them promoted apoptosis in HUVECs. All the analogues reduced the expression of E- and N-cadherin in different amounts, while the analogues-1 and -3 exhibited similar antimigratory effects on HepG2 cells. The results of this study reveal considerable potential to develop new tyrosine kinase inhibitors with improved antiplatelet and antitumor properties. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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