Ukr.Biochem.J. 2020; Volume 92, Issue 5, Sep-Oct, pp. 23-32

doi: https://doi.org/10.15407/ubj92.05.023

Selected 5-amino-1-aryl-1H-1,2,3-triazole scaffolds as promising antiproliferative agents

09.11.2020   Uncategorized   No comments

N. Pokhodylo1*, O. Shyyka1, N. Finiuk2, R. Stoika2

1Ivan Franko National University of Lviv, Ukraine;
2Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
*e-mail: pokhodylo@gmail.com; stoika@cellbiol.lviv.ua

Received: 09 January 2020; Accepted: 25 June 2020

Development of a new effective drugs with low side effects and definite chemical characteristics needs indentification of bioactive scaffolds for further structural optimization. New synthesized derivatives of 4-hetaryl-5-amino-1-aryl-1H-1,2,3-triazoles and 3H-[1,2,3]triazolo[4,5-b]pyridines were tested for anticancer activity using 60 human tumor cell lines within 9 cancer types. The selective influence of (5-amino-1H-1,2,3-triazol-4-yl)quinazolin-4(3H)-ones: 2-(5-amino-1-(4-chlorophenyl)-1H-1,2,3-triazol-4-yl)quinazolin-4(3H)-one and 2-(5-amino-1-phenyl-1H-1,2,3-triazol-4-yl)-6-bromoquinazolin-4(3H)-one on ovarian cancer OVCAR-4 cells with growth percentage (GP) = -4.08 and 6.63%, respectively, was found. The derivative  5,7-diamino-3-(3-(trifluoromethyl)phenyl)-3H-[1,2,3]triazolo[4,5-b]pyridine-6-carbonitrile possessed high activity towards lung cancer EKVX cells (GP = 29.14%). The compounds were shown to be less toxic than doxorubicin towards non-tumor human embryonic kidney cells of HEK293 line. Thus, the results of our study confirm the anticancer potential of compounds based on 5-amino-1-aryl-1H-1,2,3-triazoles scaffolds and their fused polycyclic derivatives.

Keywords: , , , , , , , , , , , ,

References:

  1.  Soltis MJ, Yeh HJ, Cole KA, Whittaker N, Wersto RP, Kohn EC. Identification and characterization of human metabolites of CAI [5-amino-1-1(4′-chlorobenzoyl-3,5-dichlorobenzyl)-1,2,3-triazole- 4-carboxamide). Drug Metab Dispos. 1996;24(7):799-806. PubMed
  2. Shi J, Chen C , Ju R , Wang Q, Li J , Guo , Ye C, Zhang D. Carboxyamidotriazole combined with IDO1-Kyn-AhR pathway inhibitors profoundly enhances cancer immunotherapy. J Immunother Cancer. 2019;7(1):246. PubMed, PubMedCentral, CrossRef
  3. Ju R, Fei K, Li S, Chen C, Zhu L, Li J, Zhang D, Guo L , Ye C. Metabolic mechanisms and a rational combinational application of carboxyamidotriazole in fighting pancreatic cancer progression after chemotherapy.  Pharmacol Exp Ther. 2018;367(1):20-27. PubMed, CrossRef
  4. Chen C, Ju R, Shi J, Chen W, Sun F, Zhu L, Li J, Zhang D, Ye C, Guo L. Carboxyamidotriazole synergizes with sorafenib to combat non-small cell lung cancer through inhibition of NANOG and aggravation of apoptosis. J Pharmacol Exp Ther. 2017;362(2):219-229. PubMed, CrossRef
  5. Moody TW, Chiles J, Moody E, Sieczkiewicz GJ, Kohn EC. CAI inhibits the growth of small cell lung cancer cells. Lung Cancer. 2003;39(3):279-288. PubMed, CrossRef
  6. Guo L, Li ZS, Wang HL, Ye CY, Zhang DC. Carboxyamido-triazole inhibits proliferation of human breast cancer cells via G(2)/M cell cycle arrest and apoptosis. Eur J Pharmacol. 2006;538(1-3):15-22. PubMed, CrossRef
  7. Pokhodylo NT, Shyyka OYa, Matiychuk VS. Synthesis and anticancer activity evaluation of new 1,2,3-triazole-4-carboxamide derivatives. Med Chem Res. 2014; 23(5): 2426–2438.  CrossRef
  8. Shyyka OYa, Pokhodylo NT, Finiuk NS. Anticancer activity evaluation of thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidines and thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine derivatives. Biopolym Сell. 2019; 35(4): 321-330.  CrossRef
  9. Thabit MG, Mostafa AS, Selim KB, Elsayed MAA, Nasr MNA. Design, synthesis and molecular modeling of phenyl dihydropyridazinone derivatives as B-Raf inhibitors with anticancer activity. Bioorg Chem. 2020;103:104148. PubMed, CrossRef
  10. Brand S, Ko EJ,  Viayna E, Thompson S, Spinks D, Thomas M, Sandberg L, Francisco  AF, Jayawardhana S, Smith VC, Jansen C, De Rycker M, Thomas J, MacLean L, Osuna-Cabello M, Riley J, Scullion P, Stojanovski L, Simeons FRC, Epemolu O, Shishikura Y , Crouch SD, Bakshi TS, Nixon CJ, Reid IH, Hill AP, Underwood TZ, Hindley SJ, Robinson SA, Kelly JM, Fiandor JM, Wyatt PG, Marco M, Miles TJ, Read KD, Gilbert IH. Discovery and Optimization of 5-Amino-1,2,3-triazole-4-carboxamide Series against Trypanosoma cruzi. J Med Chem. 2017;60(17):7284-7299. PubMed, PubMedCentral, CrossRef
  11. Mo CY, Culyba MJ, Selwood T, Kubiak JM, Hostetler ZM, Jurewicz AJ, Keller PM, Pope AJ, Quinn A, Schneck J, Widdowson KL, Kohli RM. Inhibitors of LexA Autoproteolysis and the Bacterial SOS Response Discovered by an Academic-Industry Partnership. ACS Infect Dis. 2018;4(3):349-359.
    PubMed, PubMedCentral, CrossRef
  12. Pokhodylo NT, Shyyka OYa. New cascade reaction of azides with malononitrile dimer to polyfunctional[1,2,3]triazolo[4,5-b]pyridine. Synth Comm. 2017; 47(11): 1096-1101.  CrossRef
  13. Pokhodylo NT, Shyyka OYa, Tupychak MA, Obushak MD. Selectivity in domino-reaction of ortho-carbonyl azides with malononitrile dimer leading to [1,2,3]triazolo[1,5-a]pyrimidines.  Chem Нeterocycl Сompd. 2018; 54(2): 209-212.  CrossRef
  14. Pokhodylo NT, Matiychuk VS. Synthesis of new 1,2,3-triazolo[1,5-a]quinazolinones. J Heterocycl Chem. 2010; 47(2): 415-420. CrossRef
  15. Pokhodylo NT, Matiychuk VS, Obushak MD. Synthesis of the 1H-1,2,3-triazole derivatives by the cyclization of arylazides with 1-(1,3-benzothiazol-2-yl)acetone, 1,3-benzothiazol-2-ylacetonitrile and (4-aryl-1,3-thiazol-2-yl)acetonitrile. Chem Heterocycl Compd. 2009; 45(4): 483-488. CrossRef
  16. Pokhodylo NT, Matiychuk VS, Obushak MD. Synthesis of Triazoles via Regioselective Reactions of Aryl Azides with Cyanoacetyl Pyrroles and Indoles. Synthesis. 2009;(8):1297-1300. CrossRef
  17. Pokhodylo NT, Shyyka OYa, Obushak MD. Facile and efficient one-pot procedure for thieno[2,3-e][1,2,3]triazolo[1,5-a]pyrimidines preparation. Synth Commun. 2014; 44(7): 1002-1006. CrossRef
  18. Pokhodylo NT, Shyyka OYa, Savka RD, Obushak MD. Novel Selected Tandem Transformations of the Amino and Carbonyl/Nitrile Groups in the Gewald Thiophenes.  Phosphorus Sulfur Silicon Relat Elem. 2010; 185(10): 2092-2100.   CrossRef
  19. Saraiva MT, Costa GP, Seus N, Schumacher RF, Perin G, Paixão MW, Luque R, Alves  D. Room-temperature organocatalytic cycloaddition of azides with β-keto sulfones: toward sulfonyl-1,2,3-triazoles. Org Lett. 2015;17(24):6206-6209. PubMed, CrossRef
  20. Blastik ZE, Klepetarova B, Beier P. Enamine-Mediated Azide-Ketone [3+2] Cycloaddition of Azidoperfluoroalkanes. ChemistrySelect. 2018;3(25):7045-7048. CrossRef
  21. Ramachary DB, Ramakumar K, Narayana VV. Amino acid-catalyzed cascade [3+2]-cycloaddition/hydrolysis reactions based on the push-pull dienamine platform: synthesis of highly functionalized NH-1,2,3-triazoles. Chem Eur J. 2008;14(30):9143-9147. PubMed, CrossRef
  22. Belkheira M, Abed DE, Pons JM, Bressy C. Organocatalytic synthesis of 1,2,3-triazoles from unactivated ketones and arylazides. Chem Eur J. 2011;17(46):12917-12921. PubMed, CrossRef
  23. Organocatalytic enamide-azide cycloaddition reactions: regiospecific synthesis of 1,4,5-trisubstituted-1,2,3-triazoles. Chemistry. 2011;17(13):3584-3587. PubMed, CrossRef
  24. Li W, Du Z, Huang J, Jia Q, Zhang K, Wang J. Direct access to 1,2,3-triazoles through organocatalytic 1,3-dipolar cycloaddition reaction of allyl ketones with azides. Green Chem. 2014; 16(6): 3003-3006. CrossRef
  25. Alba AN, Companyo X, Viciano M, Rios R. Organocatalytic Domino Reactions. Curr Org Chem. 2009; 13(14): 1432-1474.   CrossRef
  26. Eschenbrenner‐Lux V, Waldmann H, Kumar K. Chapter 13. Domino Reactions in Library Synthesis. In Domino Reactions: Concepts for Efficient Organic Synthesis, L.F. Tietze (Ed.). Wiley-VCH Verlag GmbH & Co. KgaA, 2014: 497-522.  CrossRef
  27. Liu X, Zu Y, Fu Y, Yao L, Gu C, Wang W, Efferth T. Antimicrobial activity and cytotoxicity towards cancer cells of Melaleuca alternifolia (tea tree) oil. Eur Food Res Technol. 2009;229(2):247-253. CrossRef
  28. Monks A, Scudiero D, Skehan P, Shoemaker R, Paull  K, Vistica D, Hose C, Langley  J, Cronise  P, Vaigro-Wolff  A, Gray-Goodrich  M, Campbell  H, Mayo J, Boyd M. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst. 1991;83(11):757-766. PubMed, CrossRef
  29. Boyd MR, Paull KD. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev Res. 1995; 34(2): 91-109.  CrossRef
  30. Boyd MR. The NCI In Vitro Anticancer Drug Discovery Screen. In: Teicher B.A. (eds) Anticancer Drug Development Guide. Cancer Drug Discovery and Development. Totowa, NJ: Humana Press, 1997: 23-43.  CrossRef
  31. Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nat Rev Cancer. 2006;6(10):813-823. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.