Prediction of biological activity of spiroquinazolone derivatives as protein kinase inhibitors FGFR1 and CK2
DOI:
https://doi.org/10.14739/2409-2932.2020.1.198175Keywords:
spiroquinazolone derivatives, protein kinase inhibitors, receptor-oriented virtual screening, techniques in vitro, biochemical phenomenaAbstract
The purpose. The search for FGFR1 and CK2 protein kinase inhibitors were performed among spiroquinazolone derivatives using receptor-oriented virtual screening and in vitro biochemical testing using the human CK2 kinase domain.
Materials and methods. The docking was performed at ATP binding sites for protein kinases CK2 and FGFR1 using the Autodock4 program. The inhibitory activity of the studied compounds against the protein kinase CK2 was determined by the inclusion of a phosphate group-containing radioactive 32P in the peptide substrate when it was phosphorylated by the kinase in the presence of γ-32P-ATP.
Results. Testing results for the selected compounds showed that when added to an IC50 concentration of 10 µM, the protein kinase residual activity was more than 45 %.
Conclusions. The results of the analysis of LogP and LogS indicated that the optimization of spiroquinazolone derivatives should be carried out in the direction of increasing the hydrophobicity of these compounds.
References
Hernandez, D. C., & Vyas, P. (2019). Oncogenic Drivers and Development. Cancer Discovery, 9(12), 1653-1655. https://doi.org/10.1158/2159-8290.cd-19-1082
Obeng, E. A., Stewart, C., & Abdel-Wahab, O. (2019). Altered RNA Processing in Cancer Pathogenesis and Therapy. Cancer Discovery, 9(11), 1493-1510. https://doi.org/10.1158/2159-8290.cd-19-0399
Xu, C. C., Li, W. L., Qiu, P. H., Xia, Y. Q., Du, X. J., Wang, F., … Li, X. K. (2015). The therapeutic potential of a novel non-ATP-competitive fibroblast growth factor receptor 1 inhibitor on gastric cancer. Anti-Cancer Drugs, 26(4), 379-387. https://doi.org/10.1097/cad.0000000000000195
Chua, M. M. J., Ortega, C. E., Sheikh, A., Lee, M., Abdul-Rassoul, H., Hartshorn, K. L., & Dominguez, I. (2017). CK2 in Cancer: Cellular and Biochemical Mechanisms and Potential Therapeutic Target. Pharmaceuticals, 10(1), Article Unsp 18. https://doi.org/10.3390/ph10010018
Andre, F., Arnedos, M., Baras, A. S., Baselga, J., Bedard, P. L., Berger, M. F., … Consortium, A. P. G. (2017). AACR Project GENIE: Powering Precision Medicine through an International Consortium. Cancer Discovery, 7(8), 818-831. https://doi.org/10.1158/2159-8290.cd-17-0151
Trembley, J. H., Wu, J. J., Unger, G. M., Kren, B. T., & Ahmed, K. (2013). CK2 suppression of apoptosis and its implication in cancer biology and therapy. Protein kinase CK2 (pp. 319-343) https://doi.org/10.1002/9781118482490.ch12
Ahmed, K., Davis, A. T., Wang, H. M., Faust, R. A., Yu, S. H., & Tawfic, S. (2000). Significance of protein kinase CK2 nuclear signaling in neoplasia. Journal of Cellular Biochemistry, 130-135.
Litchfield, D. W. (2003). Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochemical Journal, 369, 1-15. https://doi.org/10.1042/bj20021469
Ahmad, K. A., Wang, G. X., Unger, G., Slaton, J., & Ahmed, K. (2008). Protein kinase CK2-A key suppressor of apoptosis. Advances in Enzyme Regulation, Vol 48, 48, 179-187. https://doi.org/10.1016/j.advenzreg.2008.04.002
Filhol, O., Deshiere, A., & Cochet, C. (2013). Role of CK2 in the control of cell plasticity in breast carcinoma progression. Protein kinase CK2 (pp. 363-382) https://doi.org/10.1002/9781118482490.ch14
Montenarh, M. (2014). Protein Kinase CK2 and Angiogenesis. Advances in Clinical and Experimental Medicine, 23(2), 153-158. https://doi.org/10.17219/acem/37040
Sarno, S., Papinutto, E., Franchin, C., Bain, J., Elliott, M., Meggio, F., … Pinna, L. A. (2011). ATP Site-Directed Inhibitors of Protein Kinase CK2: An Update. Current Topics in Medicinal Chemistry, 11(11), 1340-1351. https://doi.org/10.2174/156802611795589638
Prykhod'ko, A. O., Dubinina, G. G., Golovach, S. M., Yarmoluk, S. M. (2004). Inhibitory proteinkinazy SK2 [Inhibitors of protein kinase CK2] Ukrainica Bioorganica Acta, (1-2), 39-48. [in Ukrainian].
Chilin, A., Battistutta, R., Bortolato, A., Cozza, G., Zanatta, S., Poletto, G., … Moro, S. (2008). Coumarin as attractive casein kinase 2 (CK2) inhibitor scaffold: An integrate approach to elucidate the putative binding motif and explain structure-activity relationships. Journal of Medicinal Chemistry, 51(4), 752-759. https://doi.org/10.1021/jm070909t
Lolli, G., Cozza, G., Mazzorana, M., Tibaldi, E., Cesaro, L., Donella-Deana, A., … Pinna, L. A. (2012). Inhibition of Protein Kinase CK2 by Flavonoids and Tyrphostins. A Structural Insight. Biochemistry, 51(31), 6097-6107. https://doi.org/10.1021/bi300531c
Syniugin, A. R., Ostrynska, O. V., Chekanov, M. O., Volynets, G. P., Starosyla, S. A., Bdzhola, V. G., & Yarmoluk, S. M. (2016). Design, synthesis and evaluation of 3-quinoline carboxylic acids as new inhibitors of protein kinase CK2. Journal of Enzyme Inhibition and Medicinal Chemistry, 31, 160-169. https://doi.org/10.1080/14756366.2016.1222584
Golub, A. G., Yakovenko, O. Y., Bdzhola, V. G., Sapelkin, V. M., Zien, P., & Yarmoluk, S. M. (2006). Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2. Journal of Medicinal Chemistry, 49(22), 6443-6450. https://doi.org/10.1021/jm050048t
Chekanov, M. O., Ostrynska, O. V., Tarnavskyi, S. S., Synyugin, A. R., Briukhovetska, N. V., Bdzhola, V. G., . . . Yarmoluk, S. M. (2014). Design, synthesis and biological evaluation of 2-aminopyrimidinones and their 6-aza-analogs as a new class of CK2 inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry, 29(5), 639-646. https://doi.org/10.3109/14756366.2013.837898
Prykhod'ko, A. O., Yakovenko, O. Y., Golub, A. G., Bdzhola, V. G., & Yarmoluk, S. M. (2005). Evaluation of 4H-4-chromenone derivatives as inhibitors of protein kinase CK2. Biopolymers and Cell, 21(3), 287-292. https://doi.org/10.7124/bc.0006F4
Chon, H. J., Bae, K. J., Lee, Y., & Kim, J. (2015). The casein kinase 2 inhibitor, CX-4945, as an anti-cancer drug in treatment of human hematological malignancies. Frontiers in Pharmacology, 6, Article 70. https://doi.org/10.3389/fphar.2015.00070
Varenichenko, S. A., Farat, O. K., Markov, V. I. (2013). Sintez novykh proizvodnykh 2-spirokhinazolonov [Synthesis of New Derivatives of 2-Spiroquinazolones]. Voprosy khimii i khimicheskoi tekhnologii, (6), 28-31. [in Russian].
Markov, V. I., & Farat, O. K. (2012). 5',6',7',8'-Tetrahydro-1'H,3'H-spiro cyclohexane-1,2'-quinazolin -4'-one in Mannich reaction. Chemistry of Heterocyclic Compounds, 48(6), 925-930. https://doi.org/10.1007/s10593-012-1078-z
Shi, D. X., Qian, D. F., Zhang, Q., & Li, J. R. (2009). Cyclohexanespiro-2'-2',3',6',7'-tetrahydro-1'H-cyclopenta d pyrimidin-4'(5'H)-one. Acta Crystallographica Section E-Crystallographic Communications, 65, O615-U2652. https://doi.org/10.1107/s1600536809005388
Upadysheva, A. V., Grigor'eva, N. D., Ryabokobylko, Yu. S., Znamenskaya, A. P. (1983). Recyclization of 2,2-disubstituted 4(3H)-oxo- and 4-chloro-1,2-dihydropyrimidines to 4-aminopyridine derivatives. Chemistry of Heterocyclic Compounds, 19(1), 95-100. https://doi.org/10.1007/BF00512825
Paleček, J., & Kuthan, J. (1974). Zur N‐Alkylierung von 1,4‐Dihydropyridinderivaten. Zeitschrift Für Chemie, 14(8), 308-309. https://doi.org/10.1002/zfch.19740140807
Markov, V. I., Farat, O. K., Varenichenko, S. A., Velikaya, E. V., Zubatyuk, R. I., & Shishkin, O. V. (2013). Synthesis and Formylation of Substituted 2-Spiropyrimidin-4-ones and Related Compounds. Chemistry of Heterocyclic Compounds, 49(8), 1158-1165. https://doi.org/10.1007/s10593-013-1358-2
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings (Reprinted from Advanced Drug Delivery Reviews, vol 23, pg 3-25, 1997). Advanced Drug Delivery Reviews, 46(1-3), 3-26. https://doi.org/10.1016/s0169-409x(00)00129-0
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