Biopolym. Cell. 2021; 37(5):389-399.
Bioorganic Chemistry
Synthesis and evaluation of biological activity of 1-[2-amino-4-methylthiazol-5-yl]-3-arylpropenones
Lozynskyi A. V., Yushyn I. M., Konechnyi Yu. T., Roman O. M., Matiykiv O. V., Smaliukh O. V., Mosula L. M., Polovkovych S. V., Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Ivan Horbachevsky Ternopil National Medical University
    1, Maidan Voli, Ternopil, Ukraine, 46001
  3. Lviv Polytechnic National University
    12, Stepan Bandera Str., Lviv, Ukraine, 79013


Aim. To accomplish the synthesis and screening of anticancer and antimicrobial activities of 1-[2-amino-4-methylthiazol-5-yl]-3-arylpropenones 2-10. Methods. The in vitro anticancer activity of compounds 4, 6, 8-10 has been established by DTP of the National Cancer Institute. The antibacterial and antifungal activities of synthesized thiazole-based derivatives were evaluated in vitro with the agar diffusion and broth microdilution methods to wards Gram-positive, Gram-negative bacteria and yeasts. For the synthesized compounds, the in silico drug-likeness screening using SwissADME online server is reported. Results. The novel 1-[2-amino-4-methylthiazol-5-yl]-3-arylpropenones were synthesized from 1-[2-amino-4-methylthiazol-5-yl]ethanones and various aromatic aldehydes in the Claisen–Schmidt condensation. The synthesized compound 9 was moderately active against the leukemia CCRF-CEM and HL-60(TB), renal cancer UO-31 and breast cancer MCF7 cell lines. The antimicrobial screening led to identification of the active compound 10 against Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Conclusions. The results obtained herein provide a platform for structure-based optimization of these newly identified thiazole-based compounds for the anticancer and antibacterial drug design.
Keywords: thiazoles, Claisen-Schmidt condensation, anticancer activity, antimicrobial activity, SwissADME


[1] Dua R, Shrivastava S, Sonwane SK, Srivastava SK. Pharmacological significance of synthetic heterocycles scaffold: a review. Adv Biol Res. 2011; 5(3):120-44.
[2] Zhou CH, Wang Y. Recent researches in triazole compounds as medicinal drugs. Curr Med Chem. 2012; 19(2):239-80.
[3] Chhabria MT, Patel S, Modi P, Brahmkshatriya PS. Thiazole: A review on chemistry, synthesis and therapeutic importance of its derivatives. Curr Top Med Chem. 2016; 16(26):2841-62.
[4] Leoni A, Locatelli A, Morigi R, Rambaldi M. Novel thiazole derivatives: a patent review (2008-2012; Part 1). Expert Opin Ther Pat. 2014; 24(2):201-16.
[5] Liu CL, Li ZM, Zhong B. Synthesis and biological activity of novel 2-methyl-4-trifluoromethyl-thiazole-5-carboxamide derivatives. J Fluor Chem. 2004; 125(9):1287-90.
[6] Gu XH, Wan XZ, Jiang B. Syntheses and biological activities of bis(3-indolyl)thiazoles, analogues of marine bis(indole)alkaloid nortopsentins. Bioorg Med Chem Lett. 1999; 9(4):569-72.
[7] Ducharme Y, Brideau C, Dube D, Chan CC, Falgueyret JP, Gillard JW, Guay J, Hutchinson JH, McFarlane CS. Naphthalenic lignan lactones as selective, non redox 5-lipoxygenase inhibitors. Synthesis and biological activity of (methoxyalkyl)thiazole and methoxytetrahydropyran hybrids. J Med Chem. 1994; 37(4):512-8.
[8] De S, Adhikari S, Tilak-Jain J, Menon VP, Devasagayam TPA. Antioxidant activity of an aminothiazole com-pound: possible mechanisms. Chem.-Biol. Interact. 2008; 173(3):215-23.
[9] Holla BS, Malini KV, Rao BS, Sarojini BK, Kumari NS. Synthesis of some new 2,4-disubstituted thiazoles as possible antibacterial and anti-inflammatory agents. Eur J Med Chem. 2003; 38(3):313-8.
[10] Kumar A, Rajput CS, Bhati SK. Synthesis of 3-[4′-(p-chlorophenyl)-thiazol-2′-yl]-2-[(substituted azetidi-none/thiazolidinone)-aminomethyl]-6-bromoquinazolin-4-ones as anti-inflammatory agent. Bioorg Med Chem. 2007; 15(8):3089-96.
[11] Manju SL. Identification and development of thiazole leads as COX-2/5-LOX inhibitors through in-vitro and in-vivo biological evaluation for anti-inflammatory activity. Bioorg Chem. 2020; 100:103882-99.
[12] Fomenko I, Lozynska I, Bondarchuk T, Denysenko N, Lesyk R, Sklyarov A. Anti-inflammatory hydrogen sulfide-releasing agents with reduced gastro- and enterotoxicity on the stress model in rats. Minerva Biotecnol. 2021; 33(2):117-24.
[13] Wilson KJ, Illig CR, Subasinghe N, Hoffman JB, Rudolph MJ, Soll R, Molloy CJ, Bone R, Green D, Randall T, Zhang M, Lewandowski FA, Zhou Z, Sharp C, Maguire D, Grasberger B, DesJarlais RL, Spurlino J. Synthesis of thiophene-2-carboxamidines containing 2-amino-thiazoles and their biological evaluation as urokinase inhibitors. Bioorg Med Chem Lett. 2001; 11(7):915-8.
[14] van Muijlwijk-Koezen JE, Timmerman H, Vollinga RC, von Drabbe Künzel JF, de Groote M., Visser S, Ijzerman AP. Thiazole and thiadiazole analogues as a novel class of adenosine receptor antagonists. J Med Chem. 2001; 44(5):749-62.
[15] Vu HN, Kim JY, Hassan AH, Choi K, Park JH, Park KD, Lee JK, Pae AN, Choo H, Min S-J, Cho YS. Synthesis and biological evaluation of picolinamides and thiazole-2-carboxamides as mGluR5 (metabotropic glutamate receptor 5) antagonists. Bioorg Med Chem Lett. 2016; 26(1):140-4.
[16] Ali SH, Sayed AR. Review of the synthesis and biological activity of thiazoles. Synth Commun. 2021; 51(5):670-700.
[17] Lesyk, RB, Zimenkovsky BS. 4-Thiazolidones: centenarian history, current status and perspectives for modern organic and medicinal chemistry. Curr Org Chem. 2004; 8(16):1547-77.
[18] Lozynskyi A, Zimenkovsky B, Gzella AK, Lesyk R. Arylidene pyruvic acids motif in the synthesis of new 2H,5H-chromeno[4′,3′:4,5]thiopyrano [2,3-d]thiazoles via tandem hetero-Diels-Alder-hemiacetal reaction. Synth Commun. 2015; 45(19):2266-70.
[19] Lozynskyi A, Holota S, Yushyn I, Sabadakh O, Karpenko O, Novikov V, Lesyk R. Synthesis and Biological Activity Evaluation of Polyfunctionalized Anthraquinonehydrazones. Lett Drug Des Discov. 2021; 18(2):199-209.
[20] Sklyarova Y, Fomenko I, Lozynska I, Lozynskyi A, Lesyk R, Sklyarov A. Hydrogen sulfide releasing 2-mercaptoacrylic acid-based derivative possesses cytoprotective activity in a small intestine of rats with medication-induced enteropathy. Sci Pharm. 2017; 85(4):35.
[21] Chebanov VA, Saraev VE, Desenko SM, Chernenko VN, Knyazeva IV, Groth U, Glasnov TN, Kappe CO. Tuning of chemo-and regioselectivities in multicomponent condensations of 5-aminopyrazoles, dimedone, and aldehydes. J Org Chem. 2008; 73(13):5110-8.
[22] Das D, Sikdar P, Bairagi M. Recent developments of 2-aminothiazoles in medicinal chemistry. Eur J Med Chem. 2016; 109:89-98.
[23] Bondock S, Albormani O, Fouda AM, Abu Safieh KA. Progress in the chemistry of 5-acetylthiazoles. Synth Commun. 2016; 46(13):1081-117.
[24] Lozynskyi A, Zimenkovsky B, Radko L, Stypula-Trebas S, Roman O, Gzella AK, Lesyk R. Synthesis and cytotox-icity of new thiazolo[4,5-b]pyridine-2(3H)-one derivatives based on α,β-unsaturated ketones and α-ketoacids. Chem Pap. 2018; 72(3):669-81.
[25] Sarkis GY, Al-Azawe S. Preparation and spectral characterization of substituted 2-aminothiazoles. J Chem Eng Data. 1973; 18(1):99-102.
[26] Shoemaker RH. The NCI60 human tumor cell line anticancer drug screen. Natl Rev Cancer. 2006; 6:813-23.
[27] Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A, Gray-Goodrich 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):757-66.
[28] 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.
[29] EUCAST. Disk Diffusion-Manual v 9.0 (1 January, 2021). Available on-line: (accessed on 20 July 2021).
[30] Balouiri M, Sadiki M, Ibnsouda S.K. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal. 2016; 6(2):71-9.
[31] Baell JB, Ferrins L, Falk H, Nikolakopoulos G. PAINS: Relevance to tool compound discovery and frag-ment-based screening. Aust J Chem. 2013; 66(12):1483-94.
[32] Wondrak GT, Cabello CM, Villeneuve NF, Zhang S, Ley S, Li Y, Sun Z, Zhang DD. Cinnamoyl-based Nrf2-activators targeting human skin cell photo-oxidative stress. Free Radic Biol Med. 2008; 45(4):385-95.
[33] McGovern SL, Caselli E, Grigorieff N, Shoichet BK. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J Med Chem. 2002; 45(8):1712-22.
[34] SwissADME. Available online: (accessed on 27 March 2021)