European Journal of Chemistry 2020, 11(3), 198-205 | doi: https://doi.org/10.5155/eurjchem.11.3.198-205.1988 | Get rights and content






  OPEN ACCESS | PEER-REVIEWED | RESEARCH ARTICLE | DOWNLOAD PDF | VIEW FULL-TEXT PDF | TOTAL VIEWS

Synthesis and pharmacological evaluation of new fluorine substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-triazino-[1,2-b][1,2,4]triazines derived as CDK2 potential inhibitors


Dina Bakhotmah (1) orcid , Fatimah Alotaibi (2,*) orcid

(1) Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21551, Saudi Arabia
(2) Department of Chemistry, Faculty of Science, Tabuk University, Tabuk, 71941, Saudi Arabia
(*) Corresponding Author

Received: 04 Apr 2020 | Revised: 16 May 2020 | Accepted: 29 May 2020 | Published: 30 Sep 2020 | Issue Date: September 2020

Abstract


New fluorine-substituted polyfunctional pyrimido-[1,2-b]-[1,2,4]triazines and [1,3,5]-triazino[1,2-b]-[1,2,4]triazines were synthesized via the reaction between 3-amino-6-(2-aminophenyl)-1,2,4-triazin-5(2H)-one with polyfunctional oxygen/sulfur/nitrogen reagents under different conditions. Structures of the target compounds were deduced by elemental analysis and spectral measurements (IR, 1H/13C NMR, and mass spectra). According to the obtained inhibitor assay results, the inhibition activity of the new fluorine-substituted 1,2,4-triazines toward CDK2 decreased in the order of compounds 3 > 8 > 9 > 6 > 13 > 15.


Keywords


Synthesis; 1,2,4-Triazine; Pyrimido-[1,2-b]-[1,2,4]triazine; [1,3,5]-Triazino[1,2-b]-[1,2,4]triazine; CDK2 enzymatic inhibitors evaluation; Fluorinated fused heterocyclic systems

Full Text:

PDF /    /


DOI: 10.5155/eurjchem.11.3.198-205.1988

Links for Article


| | | | | | |

| | | | | | |

Related Articles




Article Metrics

This Abstract was viewed 70 times | PDF Article downloaded 19 times

Funding information


Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, 21551, Saudi Arabia.

References

[1]. Abdel-Rahman, R. M.; Angawi, R. F.; Al-Mehmadi, A. R. J. Saudi Chem. Soc. 2017, 21(4), 495-503
https://doi.org/10.1016/j.jscs.2016.11.004

[2]. Bakhotmah, D. A. Polycycl. Aromat. Comp. 2019, in press, DOI: 10.1080/10406638.2019.1625066
https://doi.org/10.1080/10406638.2019.1625066

[3]. Abdel-Rahman, R. M.; Alharbi, A. S.; Alshammari, N. A.; Adnan, Y. O. Lett. Org. Chem. 2020, 17(3), 184-190.
https://doi.org/10.2174/1570178616666190718120953

[4]. Makki, M. S.; Abdel-Rahman, R. M.; Alharbi, A. S. Curr. Org. Synth. 2019, 16(1), 165-172.
https://doi.org/10.2174/1570179415666181105142247

[5]. Makki, M. S.; Dina, A. B.; Abdel-Rahman, R. M.; Aqlan, F. M. Curr. Org. Synth. 2018, 15(1), 116-125.
https://doi.org/10.2174/1570179414666170509151123

[6]. Tib, L. A.; Adibani, S. A. Int. J. Org. Chem. 2018, 8, 176-189.
https://doi.org/10.4236/ijoc.2018.81013

[7]. Makki, M. S. T.; Abdel-Rahman, R. M.; Ali, O. A. A. Asian. J. Chem. 2016, 28(4), 917-920.
https://doi.org/10.14233/ajchem.2016.19555

[8]. Makki, M. S.; Abdel-Rahman, R. M.; Aqlan, F. M. Int. J. Org. Chem. 2015, 5(3), 200-211.
https://doi.org/10.4236/ijoc.2015.53020

[9]. Makki, M. S.; Abdel-Rahman, R. M.; Khan, K. A. J. Chem. 2014, 430573, 1-14.
https://doi.org/10.1155/2014/430573

[10]. Al-Romaizan, A. N. Mediterr. J. Chem. 2019, 9(3), 249-257.
https://doi.org/10.13171/mjc93191014920aar

[11]. Aqlan, F. M.; Makki, M. S.; Abdel‐Rahman, R. M. J. Heterocyclic. Chem. 2016, 53(4), 1310-1317.
https://doi.org/10.1002/jhet.2386

[12]. Abdel-Rahman, R. M.; Makki, M. S.; Bawazir, W. A. J. Chem. 2011, 8(1), 405-414.
https://doi.org/10.1155/2011/586063

[13]. Leyla, Y. L.; Demirayak, S.; Ilgin, S.; Atli, O. Bioorg. Med. Chem. 2014, 22, 6313-6323.
https://doi.org/10.1016/j.bmc.2014.10.002

[14]. Abdel-Rahman, R. M. Farmaco 1992, 47(3), 319-326.
https://doi.org/10.1007/BF02137667

[15]. Tomachin, A. B.; Krylova, I. Zh. Org. Khim. 1986, 22, 2420-2434.

[16]. Abdel-Rahman, R. M.; Morsy, J. M.; Hanafy, F.; Amene, H. A. Pharmazie 1999, 54(9), 667-671.

[17]. Abdel-Rahman, R. M. Pharmazie 2001, 56, 18-22.

[18]. Krystof, V.; Cankar, P.; Frysova, I.; Slouka, J.; Kontopidis, G.; Dzubak, P.; Hajduch, M.; Srovnal, J.; de Azevedo, W. F.; Orsag, M.; Paprskarova, M.; Rolcik, J.; Latr, A.; Fischer, P. M.; Strnad, M. J. Med. Chem. 2006, 49(22), 6500-6509.
https://doi.org/10.1021/jm0605740

[19]. Gucky, T.; Reznickova, E.; Dzubak, P.; Hajduch, M.; Krystof, V. Monatsh. Chemie-Chem. Monthly 2010, 141(6), 709-714.
https://doi.org/10.1007/s00706-010-0314-4

[20]. Lazzaro, F.; Giannattasio, M.; Puddu, F.; Granata, M.; Pellicioli, A.; Plevani, P.; Muzi-Falconi, M. DNA Repair 2009, 8(9), 1055-1067.
https://doi.org/10.1016/j.dnarep.2009.04.022

[21]. Wohlbold, L.; Fisher, R. P. DNA Repair 2009, 8(9), 1018-1024.
https://doi.org/10.1016/j.dnarep.2009.04.009

[22]. Saloutina, L. V.; Zapevalov, A. Y.; Kodess, M. I.; Slepukhin, P. A.; Ganebnykh, I. N.; Saloutin, V. I.; Chupakhin, O. N, J. Fluorine Chem. 2019, 227, 109362, 1-9.
https://doi.org/10.1016/j.jfluchem.2019.109362

[23]. Isanbor, C.; O'Hagan, D. J. Fluorine Chem. 2006, 127, 303-319.
https://doi.org/10.1016/j.jfluchem.2006.01.011

[24]. Abdel-Rahman, R. M.; Abdel-Monem, W. R. Indian J. Chem. B 2007, 46, 838-846.

[25]. Abdel-Rahman, R. M.; Abdel-Monem, W. R. Int. J. Chem. 2006, 16, 1-14.

[26]. Javid, A.; Heravi, M. M.; Bamoharram, F.; Nikpour, M. J. Chem. 2011, 8(2), 547-552.
https://doi.org/10.1155/2011/980546

[27]. Abrahams, S. L.; Hazen, R. J.; Batson, A. G.; Phillips, A. P. J. Pharmacol. Exp. Ther. 1989, 249(2), 359-365.

[28]. Tanigawara, Y.; Aoyama, N.; Kita, T.; Shirakawa, K.; Komada, F.; Kasuga, M.; Okumura, K. Clin. Pharmacol. Ther. 1999, 66(5), 528-534.
https://doi.org/10.1016/S0009-9236(99)70017-2

[29]. Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63(11), 2363-2389.
https://doi.org/10.1016/j.tet.2006.11.001

[30]. Wolkenberg, S. E.; Wisnoski, D. D.; Leister, W. H.; Wang, Y.; Zhao, Z.; Lindsley, C. W. Org. Lett. 2004, 6(9), 1453-1456.
https://doi.org/10.1021/ol049682b

[31]. Abdel-Rahman, R. M.; El-Gendy, Z. Indian. J. Chem. B 1989, 28, 1072-1076.

[32]. Jindal, A.; Pandya, K.; Khan, I. Med. J. Armed Forces India 2015, 71(2), 178-181.
https://doi.org/10.1016/j.mjafi.2014.04.011

[33]. Tsvetkova, E.; Goss, G. Curr. Oncol. 2012, 19(Suppl 1), S45 -S51.

[34]. Maeda, H.; Khatami, M. Clin. Trans. Med. 2018, 7(1), 11-11.

[35]. Okasha, R. M.; Alsehli, M.; Ihmaid, S.; Althagfan, S. S.; El-Gaby, M. S. A.; Ahmed, H. E. A.; Afifi, T. H. Bioorg. Chem. 2019, 92, 103262, 1-15
https://doi.org/10.1016/j.bioorg.2019.103262

[36]. Roskoski, J, R. Pharmacol. Res. 2019, 139, 471-488.
https://doi.org/10.1016/j.phrs.2018.11.035

[37]. Sanchez-Martinez, C.; Lallena, M. J.; Sanfeliciano, S. G.; de Dios, A. Bioorg. Med. Chem. Lett. 2019, 29(20), 126637, 1-18.
https://doi.org/10.1016/j.bmcl.2019.126637

[38]. Liu, Q.; Gao, J.; Zhao, C.; Guo, Y.; Wang, S.; Shen, F.; Xing, X.; Luo, Y. DNA Repair 2020, 85, 102702, 1-15.
https://doi.org/10.1016/j.dnarep.2019.102702

[39]. Matthews, D. J.; Gerritsen, M. E., Targeting Protein kinases for Cancer Therapy, John Wiley & Sons Inc., Hoboken, New Jersey, 2010.
https://doi.org/10.1002/9780470555293

[40]. Senderowicz, A. M., Inhibitors of cyclin-dependent kinase modulators for cancer therapy, In Advances in Targeted Cancer Therapy, Springer, 2005.
https://doi.org/10.1201/9781420005400.ch8

[41]. Chandrappa, S.; Kavitha, C. V.; Shahabuddin, M. S.; Vinaya, K.; Ananda Kumar, C. S.; Ranganatha, S. R.; Raghavan, S. C.; Rangappa, K. S. Bioorg. Med. Chem. 2009, 17(6), 2576-2584.
https://doi.org/10.1016/j.bmc.2009.01.016

[42]. Bakhotmah, D. A. Am. J. Heterocyclic. Chem. 2019, 5(4), 76-80.

How to cite


Bakhotmah, D.; Alotaibi, F. Eur. J. Chem. 2020, 11(3), 198-205. doi:10.5155/eurjchem.11.3.198-205.1988
Bakhotmah, D.; Alotaibi, F. Synthesis and pharmacological evaluation of new fluorine substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-triazino-[1,2-b][1,2,4]triazines derived as CDK2 potential inhibitors. Eur. J. Chem. 2020, 11(3), 198-205. doi:10.5155/eurjchem.11.3.198-205.1988
Bakhotmah, D., & Alotaibi, F. (2020). Synthesis and pharmacological evaluation of new fluorine substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-triazino-[1,2-b][1,2,4]triazines derived as CDK2 potential inhibitors. European Journal of Chemistry, 11(3), 198-205. doi:10.5155/eurjchem.11.3.198-205.1988
Bakhotmah, Dina, & Fatimah Alotaibi. "Synthesis and pharmacological evaluation of new fluorine substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-triazino-[1,2-b][1,2,4]triazines derived as CDK2 potential inhibitors." European Journal of Chemistry [Online], 11.3 (2020): 198-205. Web. 30 Oct. 2020
Bakhotmah, Dina, AND Alotaibi, Fatimah. "Synthesis and pharmacological evaluation of new fluorine substituted pyrimido[1,2-b][1,2,4]triazines and [1,3,5]-triazino-[1,2-b][1,2,4]triazines derived as CDK2 potential inhibitors" European Journal of Chemistry [Online], Volume 11 Number 3 (30 September 2020)

The other citation formats (EndNote | Reference Manager | ProCite | BibTeX | RefWorks) for this article can be found online at: How to cite item


DOI Link: https://doi.org/10.5155/eurjchem.11.3.198-205.1988

| | | | | | |

| | | | | |

Save to Zotero Save to Mendeley



European Journal of Chemistry 2020, 11(3), 198-205 | doi: https://doi.org/10.5155/eurjchem.11.3.198-205.1988 | Get rights and content

Refbacks

  • There are currently no refbacks.




Copyright (c) 2020 Authors

Creative Commons License
This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at http://www.eurjchem.com/index.php/eurjchem/pages/view/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (http://www.eurjchem.com/index.php/eurjchem/pages/view/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).


© Copyright 2010 - 2020  Atlanta Publishing House LLC All Right Reserved.

The opinions expressed in all articles published in European Journal of Chemistry are those of the specific author(s), and do not necessarily reflect the views of Atlanta Publishing House LLC, or European Journal of Chemistry, or any of its employees.

Copyright 2010-2020 Atlanta Publishing House LLC. All rights reserved. This site is owned and operated by Atlanta Publishing House LLC whose registered office is 2850 Smith Ridge Trce Peachtree Cor GA 30071-2636, USA. Registered in USA.