227
Views
3
CrossRef citations to date
0
Altmetric
Review Article

Explanatory review on pyrimidine/fused pyrimidine derivatives as anticancer agents targeting Src kinase

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 1582-1614 | Received 01 Feb 2023, Accepted 30 Mar 2023, Published online: 05 May 2023

References

  • Altmann, E., Missbach, J., Green, M., Šuša, M., Wagenknecht, H.-A., & Widler, L., (2001). 7-Pyrrolidinyl-and 7-piperidinyl-5-aryl-pyrrolo [2, 3-d] pyrimidines—potent inhibitors of the tyrosine kinase c-Src. Bioorganic & Medicinal Chemistry Letters, 11(6), 853–856. https://doi.org/10.1016/s0960-894x(01)00080-4
  • Arafa, R. K., Nour, M. S., & El-Sayed, N. A. (2013). Novel heterocyclic-fused pyrimidine derivatives: Synthesis, molecular modeling and pharmacological screening. European Journal of Medicinal Chemistry, 69, 498–507. https://doi.org/10.1016/j.ejmech.2013.08.042
  • Archna, P., Chawla, A., Teli, G., Pathania, S., Singh, S., & Srivastava, V. (2023). Exploration of antioxidant, anti-inflammatory and anticancer potential of substituted 4-thiazolidinone derivatives: Synthesis, biological evaluation and docking studies. Polycyclic Aromat. Compd. (2022), 43(1), 597–618. https://doi.org/10.1080/10406638.2021.2019796
  • Barlaam, B., Fennell, M., Germain, H., Green, T., Hennequin, L., Morgentin, R., Olivier, A., Plé, P., Vautier, M., & Costello, G. (2005). New heterocyclic analogues of 4-(2-chloro-5-methoxyanilino) quinazolines as potent and selective c-Src kinase inhibitors. Bioorganic & Medicinal Chemistry Letters, 15(24), 5446–5449. https://doi.org/10.1016/j.bmcl.2005.08.106
  • Barthakur, M. G., Borthakur, M., Devi, P., Saikia, C. J., Saikia, A., Bora, U., Chetia, A., & Boruah, R. C. (2007). A novel and efficient lewis acid catalysed preparation of pyrimidines: Microwave-promoted reaction of urea and β-formyl enamides. Synlett, 2007(02), 0223–0226.
  • Bishop, J. M. (1983). Cellular oncogenes and retroviruses. Annual Review of Biochemistry, 52(1), 301–354. https://doi.org/10.1146/annurev.bi.52.070183.001505
  • Bolen, J. B., Veillette, A., Schwartz, A. M., DeSeau, V., & Rosen, N. (1987). Activation of pp60c-src protein kinase activity in human colon carcinoma. Proceedings of the National Academy of Sciences of the United States of America, 84(8), 2251–2255. https://doi.org/10.1073/pnas.84.8.2251
  • Brandvold, K. R., Steffey, M. E., Fox, C. C., & Soellner, M. B. (2012). Development of a highly selective c-Src kinase inhibitor. ACS Chemical Biology, 7(8), 1393–1398. https://doi.org/10.1021/cb300172e
  • Brown, M. T., & Cooper, J. A. (1996). Regulation, substrates and functions of src. Biochimica et Biophysica Acta, 1287(2-3), 121–149. https://doi.org/10.1016/0304-419x(96)00003-0
  • Cai, J., Sun, M., Wu, X., Chen, J., Wang, P., Zong, X., & Ji, M. (2013). Design and synthesis of novel 4-benzothiazole amino quinazolines Dasatinib derivatives as potential anti-tumor agents. European Journal of Medicinal Chemistry. 63, 702–712. https://doi.org/10.1016/j.ejmech.2013.03.013
  • Cartwright, C., Kamps, M., Meisler, A., Pipas, J., & Eckhart, W. (1989). pp60c-src activation in human colon carcinoma. The Journal of Clinical Investigation, 83(6), 2025–2033. https://doi.org/10.1172/JCI114113
  • Chhikara, B. S., Ashraf, S., Mozaffari, S., St. Jeans, N., Mandal, D., Tiwari, R. K., Ul-Haq, Z., & Parang, K. (2020). Phenylpyrazalopyrimidines as tyrosine kinase inhibitors: Synthesis. Antiproliferative Activity, and Molecular Simulations, Molecules, 25(9), 2135.,
  • Chu, X.-Q., Cao, W.-B., Xu, X.-P., & Ji, S.-J. (2017). Iron catalysis for modular pyrimidine synthesis through β-ammoniation/cyclization of saturated carbonyl compounds with amidines. The Journal of Organic Chemistry, 82(2), 1145–1154. https://doi.org/10.1021/acs.joc.6b02767
  • Cui, Z., Chen, S., Wang, Y., Gao, C., Chen, Y., Tan, C., & Jiang, Y. (2017). Design, synthesis and evaluation of azaacridine derivatives as dual-target EGFR and Src kinase inhibitors for antitumor treatment. European Journal of Medicinal Chemistry, 136, 372–381. https://doi.org/10.1016/j.ejmech.2017.05.006
  • Du, G., Rao, S., Gurbani, D., Henning, N. J., Jiang, J., Che, J., Yang, A., Ficarro, S. B., Marto, J. A., Aguirre, A. J., Sorger, P. K., Westover, K. D., Zhang, T., & Gray, N. S. (2020). Structure-based design of a potent and selective covalent inhibitor for SRC kinase that targets a P-loop cysteine. Journal of Medicinal Chemistry, 63(4), 1624–1641. https://doi.org/10.1021/acs.jmedchem.9b01502
  • Fang, F., Li, D.-D., Li, J.-R., Sun, J., Du, Q.-R., Gong, H.-B., & Zhu, H.-L. (2013). Design, synthesis, and evaluation of substituted 6-amide-4-anilinoquinazoline derivatives as c-Src inhibitors. RSC Advances, 3(48), 26230–26240. https://doi.org/10.1039/c3ra45204b
  • Fraser, C., Dawson, J. C., Dowling, R., Houston, D. R., Weiss, J. T., Munro, A. F., Muir, M., Harrington, L., Webster, S. P., Frame, M. C., Brunton, V. G., Patton, E. E., Carragher, N. O., & Unciti-Broceta, A. (2016). Rapid discovery and structure–activity relationships of pyrazolopyrimidines that potently suppress breast cancer cell growth via SRC kinase inhibition with exceptional selectivity over ABL kinase. Journal of Medicinal Chemistry, 59(10), 4697–4710. https://doi.org/10.1021/acs.jmedchem.6b00065
  • Gayon, E., Szymczyk, M., Gérard, H., Vrancken, E., & Campagne, J.-M. (2012). Stereoselective and catalytic access to β-enaminones: An entry to pyrimidines. The Journal of Organic Chemistry, 77(20), 9205–9220. https://doi.org/10.1021/jo301675g
  • Guarino, M. (2010). Src signaling in cancer invasion. Journal of Cellular Physiology, 223(1), 14–26. https://doi.org/10.1002/jcp.22011
  • Guo, W., Li, C., Liao, J., Ji, F., Liu, D., Wu, W., & Jiang, H. (2016). Transition metal free intermolecular direct oxidative C–N bond formation to polysubstituted pyrimidines using molecular oxygen as the sole oxidant. The Journal of Organic Chemistry, 81(13), 5538–5546. https://doi.org/10.1021/acs.joc.6b00867
  • Henidi, H. A., Al-Abd, A. M., Al-Abbasi, F. A., BinMahfouz, H. A., & El-Deeb, I. M. (2019). Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer. RSC Advances, 9(37), 21578–21586. https://doi.org/10.1039/c9ra03359a
  • Hennequin, L. F., Allen, J., Breed, J., Curwen, J., Fennell, M., Green, T. P., Lambert-van der Brempt, C., Morgentin, R., Norman, R. A., Olivier, A., Otterbein, L., Plé, P. A., Warin, N., & Costello, G. (2006). N-(5-Chloro-1, 3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl) ethoxy]-5-(tetrahydro-2 H-pyran-4-yloxy) quinazolin-4-amine, a novel, highly selective, orally available, dual-specific c-Src/Abl kinase inhibitor. Journal of Medicinal Chemistry, 49(22), 6465–6488. https://doi.org/10.1021/jm060434q
  • Hu, G., Place, A. T., & Minshall, R. D. (2008). Regulation of endothelial permeability by Src kinase signaling: Vascular leakage versus transcellular transport of drugs and macromolecules. Chemico-Biological Interactions, 171(2), 177–189. https://doi.org/10.1016/j.cbi.2007.08.006
  • Huang, H., Ma, J., Shi, J., Meng, L., Jiang, H., Ding, J., & Liu, H. (2010). Discovery of novel purine derivatives with potent and selective inhibitory activity against c-Src tyrosine kinase. Bioorganic & Medicinal Chemistry, 18(13), 4615–4624. https://doi.org/10.1016/j.bmc.2010.05.032
  • Huang, W.-S., Zhu, X., Wang, Y., Azam, M., Wen, D., Sundaramoorthi, R., Thomas, R. M., Liu, S., Banda, G., Lentini, S. P., Das, S., Xu, Q., Keats, J., Wang, F., Wardwell, S., Ning, Y., Snodgrass, J. T., Broudy, M. I., Russian, K., … Shakespeare, W. C. (2009). 9-(Arenethenyl) purines as dual Src/Abl kinase inhibitors targeting the inactive conformation: Design, synthesis, and biological evaluation. Journal of Medicinal Chemistry, 52(15), 4743–4756. https://doi.org/10.1021/jm900166t
  • Hubbard, S. R., & Till, J. H. (2000). Protein tyrosine kinase structure and function. Annual Review of Biochemistry, 69(1), 373–398. https://doi.org/10.1146/annurev.biochem.69.1.373
  • Irby, R. B., Mao, W., Coppola, D., Kang, J., Loubeau, J. M., Trudeau, W., Karl, R., Fujita, D. J., Jove, R., & Yeatman, T. J. (1999). Activating SRC mutation in a subset of advanced human colon cancers. Nature Genetics, 21(2), 187–190. https://doi.org/10.1038/5971
  • Jadhav, S. D., & Singh, A. (2017). Oxidative annulations involving DMSO and formamide: K2S2O8 mediated syntheses of quinolines and pyrimidines. Organic Letters, 19(20), 5673–5676. https://doi.org/10.1021/acs.orglett.7b02838
  • Jain, K., Chitre, T., Miniyar, P., Kathiravan, M., Bendre, V., Veer, V., Shahane, S., & Shishoo, C. (2006). Biological and medicinal significance of pyrimidines, Curr. Sci, 793–803.
  • Joule, J. A., Mills, K., & Smith, G. F. (2020). Heterocyclic chemistry. CRC Press.
  • Kaplan, J., Mardon, G., Bishop, J., & Varmus, H. (1988). The first seven amino acids encoded by the v-Src oncogene act as a myristylation signal: Lysine 7 is a critical determinant. Molecular and Cellular Biology, 8(6), 2435–2441. https://doi.org/10.1128/MCB.8.6.2435
  • Kappe, C. O. (1993). 100 years of the Biginelli dihydropyrimidine synthesis. Tetrahedron, 49(32), 6937–6963.
  • Liu, F., Zhang, X., Qian, Q., & Yang, C. (2020). A concise and efficient approach to 2, 6-disubstituted 4-fluoropyrimidines from α-CF3 aryl ketones. Synthesis, 52(02), 273–280. https://doi.org/10.1055/s-0039-1690248
  • Lombardo, L. J., Lee, F. Y., Chen, P., Norris, D., Barrish, J. C., Behnia, K., Castaneda, S., Cornelius, L. A. M., Das, J., Doweyko, A. M., Fairchild, C., Hunt, J. T., Inigo, I., Johnston, K., Kamath, A., Kan, D., Klei, H., Marathe, P., Pang, S., … Borzilleri, R. M. (2004). Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. Journal of Medicinal Chemistry, 47(27), 6658–6661. https://doi.org/10.1021/jm049486a
  • Lu, X.-L., Liu, X.-Y., Cao, X., & Jiao, B.-H. (2012). Novel patented SRC kinase inhibitor. Current Medicinal Chemistry, 19(12), 1821–1829. https://doi.org/10.2174/092986712800099802
  • Luo, J., Zou, H., Guo, Y., Tong, T., Ye, L., Zhu, C., Deng, L., Wang, B., Pan, Y., & Li, P. (2022). SRC kinase-mediated signaling pathways and targeted therapies in breast cancer. Breast Cancer Research, 24(1), 1–17. https://doi.org/10.1186/s13058-022-01596-y
  • Ma, Y.-C., & Huang, X.-Y. (2002). Novel regulation and function of Src tyrosine kinase. Cellular and Molecular Life Sciences CMLS, 59(3), 456–462. https://doi.org/10.1007/s00018-002-8438-2
  • Malki, W. H., Gouda, A. M., Ali, H. E., Al-Rousan, R., Samaha, D., Abdalla, A. N., Bustamante, J., Abd Elmageed, Z. Y., & Ali, H. I. (2018). Structural-based design, synthesis, and antitumor activity of novel alloxazine analogues with potential selective kinase inhibition. European Journal of Medicinal Chemistry, 152, 31–52. https://doi.org/10.1016/j.ejmech.2018.04.029
  • Manchanda, P., Parshad, B., Kumar, A., Tiwari, R. K., Shirazi, A. N., Parang, K., & Sharma, S. K. (2017). Design, synthesis, and evaluation of the kinase inhibition potential of pyridylpyrimidinylaminophenyl derivatives. Archiv Der Pharmazie, 350(3-4), 1600390. https://doi.org/10.1002/ardp.201600390
  • Mao, W., Irby, R., Coppola, D., Fu, L., Wloch, M., Turner, J., Yu, H., Garcia, R., Jove, R., & Yeatman, T. J. (1997). Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential. Oncogene, 15(25), 3083–3090. https://doi.org/10.1038/sj.onc.1201496
  • Mehta, D., & Malik, A. B. (2006). Signaling mechanisms regulating endothelial permeability. Physiol, 86(1), 279–367. https://doi.org/10.1152/physrev.00012.2005
  • Musumeci, F., Fallacara, A. L., Brullo, C., Grossi, G., Botta, L., Calandro, P., Chiariello, M., Kissova, M., Crespan, E., Maga, G., & Schenone, S. (2017). Identification of new pyrrolo [2, 3-d] pyrimidines as Src tyrosine kinase inhibitors in vitro active against Glioblastoma. European Journal of Medicinal Chemistry, 127, 369–378. https://doi.org/10.1016/j.ejmech.2016.12.036
  • Negi, P., Cheke, R. S., & Patil, V. M. (2021). Recent advances in pharmacological diversification of Src family kinase inhibitors. Egyptian Journal of Medical Human Genetics, 22(1), 1–16. https://doi.org/10.1186/s43042-021-00172-x
  • Pal, R., Kumar, B., Swamy P M, G., & Chawla, P. A. (2023). Design, synthesis of 1, 2, 4-triazine derivatives as antidepressant and antioxidant agents: In vitro, in vivo and in silico studies. Bioorganic Chemistry, 131, 106284. https://doi.org/10.1016/j.bioorg.2022.106284
  • Perera, B. G. K., & Maly, D. J. (2008). Design, synthesis and characterization of “clickable” 4-anilinoquinazoline kinase inhibitors. Molecular bioSystems, 4(6), 542–550. https://doi.org/10.1039/b720014e
  • Ple, P. A., Green, T. P., Hennequin, L. F., Curwen, J., Fennell, M., Allen, J., Lambert-Van Der Brempt, C., & Costello, G. (2004). Discovery of a new class of anilinoquinazoline inhibitors with high affinity and specificity for the tyrosine kinase domain of c-Src. Journal of Medicinal Chemistry, 47(4), 871–887. https://doi.org/10.1021/jm030317k
  • Rosen, N., Bolen, J., Schwartz, A., Cohen, P., DeSeau, V., & Israel, M. (1986). Analysis of pp60c-src protein kinase activity in human tumor cell lines and tissues. The Journal of Biological Chemistry, 261(29), 13754–13759. https://doi.org/10.1016/S0021-9258(18)67084-X
  • Roskoski, R. Jr, (2015). Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors. Pharmacological Research, 94, 9–25. https://doi.org/10.1016/j.phrs.2015.01.003
  • Sasada, T., Kobayashi, F., Sakai, N., & Konakahara, T. (2009). An unprecedented approach to 4, 5-disubstituted pyrimidine derivatives by a ZnCl2-catalyzed three-component coupling reaction. Organic Letters, 11(10), 2161–2164. https://doi.org/10.1021/ol900382j
  • Schlessinger, J. (2000). New roles for Src kinases in control of cell survival and angiogenesis. Cell, 100(3), 293–296. https://doi.org/10.1016/S0092-8674(00)80664-9
  • Schöning-Stierand, K., Diedrich, K., Fährrolfes, R., Flachsenberg, F., Meyder, A., Nittinger, E., Steinegger, R., & Rarey, M. (2020). Proteins Plus: Interactive analysis of protein–ligand binding interfaces. Nucleic Acids Research, 48(W1), W48–W53. https://doi.org/10.1093/nar/gkaa235
  • Sharma, V., Chitranshi, N., & Agarwal, A. K. (2014). Significance and biological importance of pyrimidine in the microbial world. International Journal of Medicinal Chemistry, 2014, 1–31. (). https://doi.org/10.1155/2014/202784
  • Su, L., Sun, K., Pan, N., Liu, L., Sun, M., Dong, J., Zhou, Y., & Yin, S.-F. (2018). Cyclization of ketones with nitriles under base: A general and economical synthesis of pyrimidines. Organic Letters, 20(11), 3399–3402. https://doi.org/10.1021/acs.orglett.8b01324
  • Teli, G., & Chawla, P. A. (2021). Hybridization of imidazole with various heterocycles in targeting cancer: A decade’s work. Chemistry Select, 6(19), 4803–4836. https://doi.org/10.1002/slct.202101038
  • Thomas, S. M., & Brugge, J. S. (1997). Cellular functions regulated by Src family kinases. Annual Review of Cell and Developmental Biology, 13, 513–609. https://doi.org/10.1146/annurev.cellbio.13.1.513
  • Tintori, C., Fallacara, A. L., Radi, M., Zamperini, C., Dreassi, E., Crespan, E., Maga, G., Schenone, S., Musumeci, F., Brullo, C., Richters, A., Gasparrini, F., Angelucci, A., Festuccia, C., Delle Monache, S., Rauh, D., & Botta, M. (2015). Combining X-ray crystallography and molecular modeling toward the optimization of pyrazolo [3, 4-d] pyrimidines as potent c-Src inhibitors active in vivo against neuroblastoma. Journal of Medicinal Chemistry, 58(1), 347–361. https://doi.org/10.1021/jm5013159
  • Tiwari, R. K., Brown, A., Sadeghiani, N., Shirazi, A. N., Bolton, J., Tse, A., Verkhivker, G., Parang, K., & Sun, G. (2017). Design, synthesis, and evaluation of dasatinib–amino acid and dasatinib–fatty acid conjugates as protein tyrosine kinase inhibitors. Chem Med Chem, 12(1), 86–99. https://doi.org/10.1002/cmdc.201600387
  • Volkamer, A., Griewel, A., Grombacher, T., & Rarey, M. (2010). Analyzing the topology of active sites: On the prediction of pockets and subpockets. Journal of Chemical Information and Modeling, 50(11), 2041–2052. https://doi.org/10.1021/ci100241y
  • Volkamer, A., Kuhn, D., Grombacher, T., Rippmann, F., & Rarey, M. (2012). Combining global and local measures for structure-based druggability predictions. Journal of Chemical Information and Modeling, 52(2), 360–372. https://doi.org/10.1021/ci200454v
  • World Health Organization. (2015). Cancer. http://www.who.int/cancer/en/
  • Xu, W., Doshi, A., Lei, M., Eck, M. J., & Harrison, S. C. (1999). Crystal structures of c-Src reveal features of its autoinhibitory mechanism. Mol. Cell, 3(5), 629–638. https://doi.org/10.1016/S1097-2765(00)80356-1
  • Yang, K., Dang, Q., Cai, P.-J., Gao, Y., Yu, Z.-X., & Bai, X. (2017). Reaction of aldehydes/ketones with electron-deficient 1, 3, 5-triazines leading to functionalized pyrimidines as diels–alder/retro-diels–alder reaction products: Reaction development and mechanistic studies. The Journal of Organic Chemistry, 82(5), 2336–2344. https://doi.org/10.1021/acs.joc.6b02570
  • Zhang, C.-H., Zheng, M.-W., Li, Y.-P., Lin, X.-D., Huang, M., Zhong, L., Li, G.-B., Zhang, R.-J., Lin, W.-T., Jiao, Y., Wu, X.-A., Yang, J., Xiang, R., Chen, L.-J., Zhao, Y.-L., Cheng, W., Wei, Y.-Q., & Yang, S.-Y. (2015). Design, synthesis, and structure–activity relationship studies of 3-(Phenylethynyl)-1 H-pyrazolo [3, 4-d] pyrimidin-4-amine derivatives as a new class of Src inhibitors with potent activities in models of triple negative breast cancer. Journal of Medicinal Chemistry, 58(9), 3957–3974. https://doi.org/10.1021/acs.jmedchem.5b00270

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.