Drug design: 4-thiazolidinones applications. Part 2. Pharmacological profiles

Roman Lesyk

doi:10.20883/medical.e407

Authors

Roman Lesyk Danylo Halytsky Lviv National Medical University, Ukraine https://orcid.org/0000-0002-3322-0080

DOI:

https://doi.org/10.20883/medical.e407

Keywords:

Structure-based drug design, 5-Ene-4-thiazolidinones, Thiopyrano[2,3-d]thiazoles, biological activity, SAR analysis, Michael acceptors

Abstract

Following of the chemical diversity of 4-thiazolidinones the in-house library of new heterocycles have been designed and synthesized (more 7000 compounds). Anticancer, antitrypanosomal, antituberculosis and antiviral activity screening led to SAR database formation; lead-compounds identification; design of focused sub-libraries; formation and validation of hypotheses for structure optimization: i) complications of C5 fragment and/or functionalization of N3 position; ii) creation of the hybrid molecules; iii) fixation of 5-ene-4-thiazolidinones in fused heterocycles via annulation (thiopyrano[2,3-d]thiazoles were found as a cyclic isosteric mimetics of 5-ene-4-thiazolidinones); iv) the leukemia panel was detected to be the most sensitive among all cancer cell lines. Following the in silico and pharmacological data for the investigation of molecular mechanism of anticancer effect the argument in favor of the apoptotic related and mild prooxidant actions for active compounds have been found.

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References

Lesyk RB, Zimenkovsky BS, Kaminskyy DV, Kryshchyshyn AP, Havryluk DY, Atamanyuk DV, Subtel'na IY, Khyluk DV. Thiazolidinone motif in anticancer drug discovery. Experience of DH LNMU medicinal chemistry scientific group. Biopolymers and Cell. 2011 Mar 20;27(2):107-117. https://doi.org/10.7124/bc.000089

Devinyak O, Zimenkovsky B, Lesyk R. Biologically Active 4-Thiazolidinones: A Review of QSAR Studies and QSAR Modeling of Antitumor Activity. Current Topics in Medicinal Chemistry. 2013 Mar 1;12(24):2763-2784. https://doi.org/10.2174/1568026611212240006

Devinyak O, Havrylyuk D, Zimenkovsky B, Lesyk R. Computational Search for Possible Mechanisms of 4-Thiazolidinones Anticancer Activity: The Power of Visualization. Molecular Informatics. 2014 Mar;33(3):216-229. https://doi.org/10.1002/minf.201300086

Lesyk R, Vladzimirska O, Zimenkovsky B, Golota S, Nektgayev I, Cherpak O, Leb'yak M, Kozak O. Synthesis and antiinflammatory activity of novel 3-(2,3-dimethyl-1-phenyl-4-pyrazolon-5-yl)-4-thiazolidones. Boll Chim Farm. 2002 May-Jun;141(3):197-201. PMID 12197418

Lesyk R, Vladzimirska O, Zimenkovsky B, Horishny V, Nektegayev I, Solyanyk V, Vovk O. New thiazolidones-4 with pyrazolone-5 substituent as the potential NSAIDs. Boll Chim Farm. 1998 Jun;137(6):210-7. PMID 9713155

Zimenkovskii BS, Kutsyk RV, Lesyk RB, Matyichuk VS, Obushak ND, Klyufinska TI. Synthesis and antimicrobial activity of 2,4-dioxothiazolidine-5-acetic acid amides. Pharmaceutical Chemistry Journal. 2006 Jun;40(6):303-306. https://doi.org/10.1007/s11094-006-0115-6

Lesyk R, Pinyazhko O, Myronenko S, Nektegayev I. 5-(3-Nitrobenzylidene)-2-(thiazol-2-ylimino)-4-thiazolidinone exhibiting anticonvulsant effect. Disclosure 12.10.2015.. 2016 Mar 10; UA 105330 (Ukraine).

Nektegayev I, Lesyk R. ChemInform Abstract: 3-Oxyaryl-2-thionethiazolidones-4 and Their Choleretic Activity. Scientia Pharmaceutica. 2010 Mar;67(10):227-30. https://doi.org/10.1002/chin.200010126

Boyd MR, Paull KD. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Development Research. 1995 Feb;34(2):91-109. https://doi.org/10.1002/ddr.430340203

Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nature Reviews Cancer. 2006 Oct;6(10):813-823. https://doi.org/10.1038/nrc1951

Paull KD, Shoemaker RH, Hodes L, Monks A, Scudiero DA, Rubinstein L, Plowman J, Boyd MR. Display and Analysis of Patterns of Differential Activity of Drugs Against Human Tumor Cell Lines: Development of Mean Graph and COMPARE Algorithm. JNCI Journal of the National Cancer Institute. 1989 Jul 19;81(14):1088-1092. https://doi.org/10.1093/jnci/81.14.1088

Havrylyuk D, Mosula L, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. Synthesis and anticancer activity evaluation of 4-thiazolidinones containing benzothiazole moiety. European Journal of Medicinal Chemistry. 2010 Nov;45(11):5012-5021. https://doi.org/10.1016/j.ejmech.2010.08.008

Kaminskyy D, den Hartog GJ, Wojtyra M, Lelyukh M, Gzella A, Bast A, Lesyk R. Antifibrotic and anticancer action of 5-ene amino/iminothiazolidinones. European Journal of Medicinal Chemistry. 2016 Apr;112:180-195. https://doi.org/10.1016/j.ejmech.2016.02.011

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. European Journal of Medicinal Chemistry. 2016 Jul;117:33-46. https://doi.org/10.1016/j.ejmech.2016.03.089

Kaminskyy D, Khyluk D, Vasylenko O, Zaprutko L, Lesyk R. A Facile Synthesis and Anticancer Activity Evaluation of Spiro[Thiazolidinone-Isatin] Conjugates. Scientia Pharmaceutica. 2011;79(4):763-777. https://doi.org/10.3797/scipharm.1109-14

Havrylyuk D, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity. Journal of Medicinal Chemistry. 2012 Oct 9;55(20):8630-8641. https://doi.org/10.1021/jm300789g

Kaminskyy D, Zimenkovsky B, Lesyk R. Synthesis and in vitro anticancer activity of 2,4-azolidinedione-acetic acids derivatives. European Journal of Medicinal Chemistry. 2009 Sep;44(9):3627-3636. https://doi.org/10.1016/j.ejmech.2009.02.023

Havrylyuk D, Zimenkovsky B, Lesyk R. Synthesis and Anticancer Activity of Novel Nonfused Bicyclic Thiazolidinone Derivatives. Phosphorus, Sulfur, and Silicon and the Related Elements. 2009 Mar 10;184(3):638-650. https://doi.org/10.1080/10426500802247563

Subtel’na I, Atamanyuk D, Szymańska E, Kieć-Kononowicz K, Zimenkovsky B, Vasylenko O, Gzella A, Lesyk R. Synthesis of 5-arylidene-2-amino-4-azolones and evaluation of their anticancer activity. Bioorganic & Medicinal Chemistry. 2010 Jul;18(14):5090-5102. https://doi.org/10.1016/j.bmc.2010.05.073

Havrylyuk D, Kovach N, Zimenkovsky B, Vasylenko O, Lesyk R. Synthesis and Anticancer Activity of Isatin-Based Pyrazolines and Thiazolidines Conjugates. Archiv der Pharmazie. 2011 Jun 16;344(8):514-522. https://doi.org/10.1002/ardp.201100055

Avdieiev S, Gera L, Havrylyuk D, Hodges RS, Lesyk R, Ribrag V, Vassetzky Y, Kavsan V. Bradykinin antagonists and thiazolidinone derivatives as new potential anti-cancer compounds. Bioorganic & Medicinal Chemistry. 2014 Aug;22(15):3815-3823. https://doi.org/10.1016/j.bmc.2014.06.046

Kaminskyy D, Subtel’na I, Zimenkovsky B, Karpenko O, Gzella A, Lesyk R. Synthesis and Evaluation of Anticancer Activity of 5-Ylidene-4- Aminothiazol-2(5H)-one Derivatives. Medicinal Chemistry. 2015 Jul 24;11(6):517-530. https://doi.org/10.2174/1573406411666150211112049

Szychowski KA, Leja ML, Kaminskyy DV, Binduga UE, Pinyazhko OR, Lesyk RB, Gmiński J. Study of novel anticancer 4-thiazolidinone derivatives. Chemico-Biological Interactions. 2017 Jan;262:46-56. https://doi.org/10.1016/j.cbi.2016.12.008

Szychowski KA, Leja ML, Kaminskyy DV, Kryshchyshyn AP, Binduga UE, Pinyazhko OR, Lesyk RB, Tobiasz J, Gmiński J. Anticancer properties of 4-thiazolidinone derivatives depend on peroxisome proliferator-activated receptor gamma (PPARγ). European Journal of Medicinal Chemistry. 2017 Dec;141:162-168. https://doi.org/10.1016/j.ejmech.2017.09.071

Szychowski KA, Kaminskyy DV, Leja ML, Kryshchyshyn AP, Lesyk RB, Tobiasz J, Wnuk M, Pomianek T, Gmiński J. Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one. Scientific Reports. 2019 Jul 23;9(1). https://doi.org/10.1038/s41598-019-47177-6

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, and Silicon and the Related Elements. 2016 Mar 30;191(9):1245-1249. https://doi.org/10.1080/10426507.2016.1166108

Kryshchyshyn AP, Atamanyuk DV, Kaminskyy DV, Grellier P, Lesyk RB. Investigation of anticancer and anti-parasitic activity of thiopyrano[2,3-d]thiazoles bearing norbornane moiety. Biopolymers and Cell. 2017 Jun 30;33(3):183-205. https://doi.org/10.7124/bc.00094f

Atamanyuk D, Zimenkovsky B, Lesyk R. Synthesis and anticancer activity of novel thiopyrano[2,3-d]thiazole-based compounds containing norbornane moiety. Journal of Sulfur Chemistry. 2008 Apr;29(2):151-162. https://doi.org/10.1080/17415990801911723

Atamanyuk D. Synthesis and Biological Activity of New Thiopyrano[2,3-d]thiazoles Containing a Naphthoquinone Moiety. Scientia Pharmaceutica. 2013;81(2):423-436. https://doi.org/10.3797/scipharm.1301-13

Zelisko NI, Finiuk NS, Shvets VM, Medvid YO, Stoika RS, Lesyk RB. Screening of spiro-substituted thiopyrano[2,3-d]thiazoles for their cytotoxic action on tumor cells. Biopolymers and Cell. 2017 Aug 31;33(4):282-290. https://doi.org/10.7124/bc.00095a

Zimenkovsky B, Devinyak O, Havrylyuk D, Lesyk R. Analysis of antitumor activity of 4-thiazolidinone derivatives and their classification by probable mechanisms of action using mathematical statistics. Journal of Organic and Pharmaceutical Chemistry. 2011;9(3):64-71.

Zimenkovsky B, Devinyak O, Lesyk R. The study of the «structure – anticancer activity» relationship of 4-thiazolidinones using regression analysis and classification modeling. Journal of Organic and Pharmaceutical Chemistry. 2012;2:43-9.

Devinyak O, Lesyk R. Investigation of the relationship between the structure of 4-thiazolidinones and their antitumor activity by multidimensional adaptive regression splines. Journal of Organic and Pharmaceutical Chemistry. 2013;11(3):62-7.

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. European Journal of Medicinal Chemistry. 2016 Jul;117:33-46. https://doi.org/10.1016/j.ejmech.2016.03.089

Chumak V, Fil M, Panchuk R, Zimenkovsky B, Havrylyuk D, Lesyk R, Stoika R. Study of antineoplastic action of novel isomeric derivatives of 4-thiazolidinone. Ukrainskiĭ biokhimicheskiĭ zhurnal. 2014;86:96-105.

Коbylinska LI, Boiko NM, Panchuk RR, Grytsyna II, Klyuchivska OY, Biletska LP, Lesyk RB, Zіmenkovsky BS, Stoika RS. Putative anticancer potential of novel 4-thiazolidinone derivatives: cytotoxicity toward rat C6 glioma in vitro and correlation of general toxicity with the balance of free radical oxidation in rats. Croatian Medical Journal. 2016 Apr;57(2):151-163. https://doi.org/10.3325/cmj.2016.57.151

Havrylyuk D, Zimenkovsky B, Lesyk R, Stoika R, Lutsyk M, Panchuk R. 5-[2-Chloro-3-(4-nitrophenyl)-allylidene]-4-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-5H-thiazol-2-ones exhibiting antitumor activity in vitro and in vivo, and their solubilization method. Disclosure 21.08.2013. 2015 Jul 27; UA 109177 (Ukraine).

Zimenkovsky B, Devinyak O, Lesyk R. Modeling of a possible pharmacophore group for 4-thiazolidinones with the anticancer activity (Моделювання можливої фармакофорної групи 4-тіазолідинонів з протипухлинною активністю). Журнал органічної та фармацевтичної хімії. 2012;10:76-82.

Zimenkovsky BS, Lesyk RB, Devinyak OT, Havrylyuk DY. Method for antitumor activity predicting of 4-thiazolidinone derivatives. Disclosure 18.12.2012. 2013 May 27; UA 80435 (Ukraine).

Ouyang G, Cai X, Chen Z, Song B, Bhadury PS, Yang S, Jin L, Xue W, Hu D, Zeng S. Synthesis and Antiviral Activities of Pyrazole Derivatives Containing an Oxime Moiety. Journal of Agricultural and Food Chemistry. 2008 Nov 12;56(21):10160-10167. https://doi.org/10.1021/jf802489e

Havrylyuk D, Zimenkovsky B, Vasylenko O, Lesyk R. Synthesis and Anticancer and Antiviral Activities of New 2-Pyrazoline-Substituted 4-Thiazolidinones. Journal of Heterocyclic Chemistry. 2013 Feb;50(S1):E55-E62. https://doi.org/10.1002/jhet.1056

Zelisko NI, Demchuk I, Lesyk R. New thiopyrano[2,3-d][1,3]thiazole derivatives as potential antiviral agents. The Ukrainian Biochemical Journal. 2016 Jun 30;88(Special Issue):105-112. https://doi.org/10.15407/ubj88.si01.105

Havrylyuk D, Zimenkovsky B, Vasylenko O, Day CW, Smee DF, Grellier P, Lesyk R. Synthesis and biological activity evaluation of 5-pyrazoline substituted 4-thiazolidinones. European Journal of Medicinal Chemistry. 2013 Aug;66:228-237. https://doi.org/10.1016/j.ejmech.2013.05.044

Wojtyra MN, Lesyk RB, Zimenkovsky BS, Grellier P. (Z)-(5-[5-(3,5-diaryl-4,5-dihydropyrazol-1-yl-methylidene)-3-(pyridine-3-yl)-2-thioxothiazolidin-4-ones exhibiting antitrypanosomal action. Disclosure 18.04.2017. 2017 Oct 10; UA 119822 (Ukraine).

Holota S, Kryshchyshyn A, Derkach H, Trufin Y, Demchuk I, Gzella A, Grellier P, Lesyk R. Synthesis of 5-enamine-4-thiazolidinone derivatives with trypanocidal and anticancer activity. Bioorganic Chemistry. 2019 May;86:126-136. https://doi.org/10.1016/j.bioorg.2019.01.045

Kryshchyshyn A, Kaminskyy D, Karpenko O, Gzella A, Grellier P, Lesyk R. Thiazolidinone/thiazole based hybrids – New class of antitrypanosomal agents. European Journal of Medicinal Chemistry. 2019 Jul;174:292-308. https://doi.org/10.1016/j.ejmech.2019.04.052

Zelisko N, Karpenko O, Muzychenko V, Gzella A, Grellier P, Lesyk R. trans -Aconitic acid-based hetero -Diels-Alder reaction in the synthesis of thiopyrano[2,3- d ][1,3]thiazole derivatives. Tetrahedron Letters. 2017 May;58(18):1751-1754. https://doi.org/10.1016/j.tetlet.2017.03.062

Zelisko N, Atamanyuk D, Vasylenko O, Grellier P, Lesyk R. Synthesis and antitrypanosomal activity of new 6,6,7-trisubstituted thiopyrano[2,3-d][1,3]thiazoles. Bioorganic & Medicinal Chemistry Letters. 2012 Dec;22(23):7071-7074. https://doi.org/10.1016/j.bmcl.2012.09.091