Biopolym. Cell. 2017; 33(4):282-290.
http://dx.doi.org/10.7124/bc.00095A
Bioorganic Chemistry
Screening of spiro-substituted thiopyrano[2,3-d]thiazoles for their cytotoxic action on tumor cells
1Zelisko N. I., 2Finiuk N. S., 3Shvets V. M., Medvid Yu. O., 2Stoika R. S., 1Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Institute of Cell Biology, NAS of Ukraine
    14/16, Drahomanov Str., Lviv, Ukraine, 79005
  3. Zaporizhia State Medical University
    26, Mayakovsky avenue, Zaporizhzhia, Ukraine, 69035

Abstract

Aim. To evaluate the in vitro cytotoxicity of novel spiro-substituted thiopyrano[2,3-d]thiazoles towards tumor cells of different tissue origin. Methods. Organic synthesis; spectral methods; MTT test, statistical analysis. Results. In vitro screening of the cytotoxic activity of the 5’-carboxy-7’-aryl-1-aryl-3’,7’-dihydro-2H,2’H,5H-spiro[pyrolidin-3,6’-thiopyrano[2,3-d]thiazol]-2,2’,5-triones and N-(4-chlorophenyl)-2-[1-(4-chlorophenyl)-2,5-dioxopyrrolidin-3-ylidene]-acetamide was performed using various cancer cell lines (Jurkat human acute T-cell leukemia cell line, MCF-7 human breast adenocarcinoma cell line, Skov3 human ovarian carcinoma cells line, SK-Mel-28 human melanoma cells line, and SW-1573 human non-small-cell lung cancer cell line). The tested compounds possessed different cytotoxic action towards the studied tumor cells. Leukemia cells appeared to be more sensitive for the studied derivatives. The cytotoxic effect of the compound 2 towards Jurkat cells was shown to be dose- and time-dependent (3, 6, 24, 48 and 72 h). This compound demonstrated the cytotoxic action towards Jurkat cells as soon as in 6 h after its addition to the cultured cells (IC50 = 66 μM), and its toxicity towards these cells was more prominent after 24 h treatment (IC50= 40 μM). Conclusions. The panel of thiopyrano[2,3-d]thiazole derivatives was synthesized and screened for their cytotoxic activity in vitro towards tumor cells of different tissue origin. The compound 2 was found to be the most active agent with selectivity for the leukemia cells. This compound inhibits growth of the human acute T-cell leukemia cells of Jurkat line (IC50 = 33.5 μM) and possesses relatively low toxicity towards the pseudo-normal mammalian cells.
Keywords: thiopyrano[2,3-d]thiazoles, cytotoxic activity
Full text: (PDF, in English)

References

[1] Michael CP, Donald CD, Carl EF. The Chemotherapy Source Book. Philadelphia: Walters Kluwer. Lippincott Williams & Wilkins. 2012; 248 p.
[2] Cancer: Principles and Practice of Oncology. 6th eds. Eds DeVita, Vincent T. et al, Philadelphia, PA: Lippincott, Williams & Wilkins, 2001.
[3] Chumak VV, Fil MR, Panchuk RR, Zimenkovsky BS, Havrylyuk DY, Lesyk RB, Stoika RS. Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone. Ukr Biochem J. 2014;86(6):96-105.
[4] Crascì L, Vicini P, Incerti M, Cardile V, Avondo S, Panico A. 2-Benzisothiazolylimino-5-benzylidene-4-thiazolidinones as protective agents against cartilage destruction. Bioorg Med Chem. 2015;23(7):1551-6.
[5] Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. Synthesis of new 4-thiazolidinone-, pyrazoline-, and isatin-based conjugates with promising antitumor activity. J Med Chem. 2012;55(20):8630-41.
[6] Havrylyuk D, Zimenkovsky B, Karpenko O, Grellier P, Lesyk R. Synthesis of pyrazoline-thiazolidinone hybrids with trypanocidal activity. Eur J Med Chem. 2014;85:245-54.
[7] Senkiv J, Finiuk N, Kaminskyy D, Havrylyuk D, Wojtyra M, Kril I, Gzella A, Stoika R, Lesyk R. 5-Ene-4-thiazolidinones induce apoptosis in mammalian leukemia cells. Eur J Med Chem. 2016;117:33-46.
[8] Atamanyuk D, Zimenkovsky B, Atamanyuk V, Lesyk R. 5-Ethoxymethylidene-4-thioxo-2-thiazolidinone as ver-satile building block for novel biorelevant small molecules with thiopyrano[2,3-d][1,3]thiazole core. Synth Commun. 2014;44(2):237–244.
[9] Chen S, Chen L, Le NT, Zhao C, Sidduri A, Lou JP, Michoud C, Portland L, Jackson N, Liu JJ, Konzelmann F, Chi F, Tovar C, Xiang Q, Chen Y, Wen Y, Vassilev LT. Synthesis and activity of quinolinyl-methylene-thiazolinones as potent and selective cyclin-dependent kinase 1 inhibitors. Bioorg Med Chem Lett. 2007;17(8):2134-8.
[10] Carter PH, Scherle PA, Muckelbauer JK, Voss ME, Liu RQ, Thompson LA, Tebben AJ, Solomon KA, Lo YC, Li Z, Strzemienski P, Yang G, Falahatpisheh N, Xu M, Wu Z, Farrow NA, Ramnarayan K, Wang J, Rideout D, Yalamoori V, Domaille P, Underwood DJ, Trzaskos JM, Friedman SM, Newton RC, Decicco CP. Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-alpha. Proc Natl Acad Sci U S A. 2001;98(21):11879-84.
[11] Zhou H, Wu S, Zhai S, Liu A, Sun Y, Li R, Zhang Y, Ekins S, Swaan PW, Fang B, Zhang B, Yan B. Design, synthesis, cytoselective toxicity, structure-activity relationships, and pharmacophore of thiazolidinone derivatives targeting drug-resistant lung cancer cells. J Med Chem. 2008;51(5):1242-51.
[12] Zelisko N, Atamanyuk D, Vasylenko O, Bryhas A, Matiychuk V, Gzella A, Lesyk R. Crotonic, cynnamic, and propiolic acids motifs in the synthesis of thiopyrano[2,3-d][1,3]thiazoles via hetero-Diels–Alder reaction and re-lated tandem processes. Tetrahedron. 2014;70(3):720–9.
[13] Zelisko N, Atamanyuk D, Ostapiuk Y, Bryhas A, Matiychuk V, Gzella A, Lesyk R. Synthesis of fused thiopyrano [2, 3-d][1, 3] thiazoles via hetero-Diels–Alder reaction related tandem and domino processes. Tetrahedron. 2015;71:9501–9508.
[14] Kowiel M, Zelisko N, Atamanyuk D, Lesyk R, Gzella AK. 2-[7-(3,5-Dibromo-2-hy­droxy­phen­yl)-6-eth­oxy­carbonyl-2-oxo-5H-2,3,6,7-tetra­hydro­thio­pyrano[2,3-d][1,3]thia­zol-6-yl]acetic acid ethanol monosolvate. Acta Crystallographica Section E: Structure Reports Online. 2012;68(Pt 9):2721-2.
[15] Lesyk R, Zimenkovsky B, Atamanyuk D, Jensen F, Kieć-Kononowicz K, Gzella A. Anticancer thiopyrano[2,3-d][1,3]thiazol-2-ones with norbornane moiety. Synthesis, cytotoxicity, physico-chemical properties, and computational studies. Bioorg Med Chem. 2006;14(15):5230-40.
[16] Atamanyuk D, Zimenkovsky B, Lesyk R. Synthesis and anticancer activity of novel thiopyrano[2.3-d]thiazole-based compounds containing norbornane moiety. J Sulf Chem. 2008;29(2):151–62.
[17] Kaminskyy D, Vasylenko O, Atamanyuk D, Gzella A, Lesyk R. Isorhodanine and thiorhodanine motifs in the synthesis of fused thiopyrano [2,3-d][1,3]thiazoles. Synlett. 2011;10(10):1385–8. 10.1055/s-0030-1260765
[18] Kryshchyshyn A, Atamanyuk D, Lesyk R. Fused Thiopyrano[2,3-d]thiazole Derivatives as Potential Anticancer Agents. Sci Pharm. 2012;80(3):509-29.
[19] Lozynskyi A, Zimenkovsky B, Lesyk R. Synthesis and Anticancer Activity of New Thiopyrano[2,3-d]thiazoles Based on Cinnamic Acid Amides. Sci Pharm. 2014;82(4):723-33. PubMed PMID: 26171321;
[20] Zelisko N, Atamanyuk D, Vasylenko O, Grellier P, Lesyk R. Synthesis and antitrypanosomal activity of new 6,6,7-trisubstitutedthiopyrano[2,3-d][1,3]thiazoles. Bioorg Med Chem Lett. 2012;22(23):7071–4.
[21] Atamanyuk D, Zimenkovsky B, Atamanyuk V, Nektegayev I, Lesyk R. Synthesis and biological activity of new thiopyrano[2,3-d]thiazoles containing a naphthoquinone moiety. Sci Pharm. 2013;81(2):423–36.
[22] Zelisko N, Karpenko O, Muzychenko V, Gzella A, Grellier Ph, Lesyk R. Trans-aconitic acid-based hetero-Diels-Alder reaction in the synthesis of thiopyrano[2,3-d][1,3]thiazole derivatives. Tetrahedron Lett. 2017;58(18):1751–4.
[23] Lozynskyi A, Golota S, Zimenkovsky B, Atamanyuk D, Gzella A, Lesyk R. Synthesis, anticancer and antiviral activities of novel thiopyrano[2,3-d]thiazole-6-carbaldehydes. Phosphorus Sulfur Silicon Relat Elem. 2016;191(9):1245-9.
[24] Liu X, Zu YG, Fu YJ, Yao LP, Gu CB, Wang W, Efferth T. Antimicrobial activity and cytotoxicity towards cancer cells of Melaleuca alternifolia (tea tree) oil. Eur Food Res Technol. 2009;229:247–53.
[25] Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. Synthesis of new 4-thiazolidinone-, pyrazoline-, and isatin-based conjugates with promising antitumor activity. J Med Chem. 2012;55(20):8630-41.