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Article

Synthesis, In Vitro and In Silico Anticancer Activity of New 4-Methylbenzamide Derivatives Containing 2,6-Substituted Purines as Potential Protein Kinases Inhibitors

Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 5/2 Academician V.F. Kuprevich Street, BY-220141 Minsk, Belarus
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Academic Editors: Alessio Nocentini, Wagdy M. Eldehna and Stanislav Kalinin
Int. J. Mol. Sci. 2021, 22(23), 12738; https://doi.org/10.3390/ijms222312738
Received: 1 November 2021 / Revised: 18 November 2021 / Accepted: 19 November 2021 / Published: 25 November 2021
(This article belongs to the Special Issue Activity, Function and Druggability of Cancer-Related Enzymes)
A novel class of potential protein kinase inhibitors 716 was synthesized in high yields using various substituted purines. The most promising compounds, 7 and 10, exhibited inhibitory activity against seven cancer cell lines. The IC50 values for compounds 7 and 10 were 2.27 and 2.53 μM for K562 cells, 1.42 and 1.52 μM for HL-60 cells, and 4.56 and 24.77 μM for OKP-GS cells, respectively. In addition, compounds 7 and 10 dose-dependently induced the apoptosis and cell cycle arrest at G2/M phase, preventing the cell division of OKP-GS cells. Compounds 7, 9, and 10 showed 36–45% inhibitory activity against PDGFRα and PDGFRβ at the concentration of 1 μM. Molecular modeling experiments showed that obtained compounds could bind to PDGFRα as either type 1 (compound 7, ATP-competitive) or type 2 (compound 10, allosteric) inhibitors, depending on the substituent in the amide part of the molecule. View Full-Text
Keywords: purine derivatives; anticancer activity; protein kinase inhibitors; cellular apoptosis; molecular docking purine derivatives; anticancer activity; protein kinase inhibitors; cellular apoptosis; molecular docking
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MDPI and ACS Style

Kalinichenko, E.; Faryna, A.; Bozhok, T.; Panibrat, A. Synthesis, In Vitro and In Silico Anticancer Activity of New 4-Methylbenzamide Derivatives Containing 2,6-Substituted Purines as Potential Protein Kinases Inhibitors. Int. J. Mol. Sci. 2021, 22, 12738. https://doi.org/10.3390/ijms222312738

AMA Style

Kalinichenko E, Faryna A, Bozhok T, Panibrat A. Synthesis, In Vitro and In Silico Anticancer Activity of New 4-Methylbenzamide Derivatives Containing 2,6-Substituted Purines as Potential Protein Kinases Inhibitors. International Journal of Molecular Sciences. 2021; 22(23):12738. https://doi.org/10.3390/ijms222312738

Chicago/Turabian Style

Kalinichenko, Elena, Aliaksandr Faryna, Tatyana Bozhok, and Alesya Panibrat. 2021. "Synthesis, In Vitro and In Silico Anticancer Activity of New 4-Methylbenzamide Derivatives Containing 2,6-Substituted Purines as Potential Protein Kinases Inhibitors" International Journal of Molecular Sciences 22, no. 23: 12738. https://doi.org/10.3390/ijms222312738

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