Biopolym. Cell. 2021; 37(2):153-164.
Bioorganic Chemistry
Antimicrobial and cytotoxic activities of thiazolo[4,5-b]pyridine derivatives
1Lozynskyi A. V., 2Derkach H. O., 2Zasidko V. V., 1Konechnyi Y. T., 3Finiuk N. S., 4Len Y. T., 2Kutsyk R. V., 1Regeda M. S., 1, 5Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Ivano-Frankivsk National Medical Universitу
    2, Halytska Str., Ivano-Frankivsk, Ukraine, 76018
  3. Institute of Cell Biology, NAS of Ukraine
    14/16, Drahomanov Str., Lviv, Ukraine, 79005
  4. Lviv Scientific research forensic center of the Ministry of Internal Affairs of Ukraine
    24, Konyushynna Str., Lviv, Ukraine, 79040
  5. University of Information Technology and Management in Rzeszow
    2, Sucharskiego Str., Rzeszow, Poland, 35-225

Abstract

Aim. The screening of antimicrobial and cytotoxic activities of thiazolo[4,5-b]pyridine derivatives was accomplished. Methods. The antibacterial and antifungal activities of synthesized thiazolopyridines were evaluated in vitro with the agar diffusion and broth microdilution methods using clinical and reference strains of Gram-positive, Gram-negative bacteria and yeasts. The structure-antibacterial/antifungal activity relationships of the screened compounds were established. The target compounds were screened for their cytotoxicity effects on HaCaT and HEK293 cells using MTT assay. Results. The highest antimicrobial activity was observed for compound V 2-oxo-7-thiophen-2-yl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid with minimal inhibitory concentration (MIC) 12.5 μg/mL against Candida albicans. At the same time, the synthesized compounds were explored in the interaction with amoxicillin against multidrug resistant clinical isolates of ESβL+ Klebsiella pneumonie and Staphylococcus haemolyticus (MRSH). The best synergistic activity with amoxicillin was exhibited by compound VI. HaCaT human keratinocytes and HEK293 human embryonic kidney cells demonstrated resistance to the thiazolopyridine derivatives treatment and did not reach the IC50 value up to 100 µM. Conclusions. The tested thiazolopyridines constitute an interesting background for further development of new chemotherapeutic agents.
Keywords: heterocyclic compounds, thiazolidinones, thiazolo[4,5-b]pyridines, antimicrobial activity, antiproliferative activity

References

[1] Gomtsyan A. Heterocycles in drugs and drug discovery. Chem Heterocycl Compd. 2012; 48(1):7-10.
[2] Baumann M, Baxendale IR, Ley SV. The flow synthesis of heterocycles for natural product and medicinal chemistry applications. Mol Divers. 2011; 15(3):613-630.
[3] Dilek Altıntop M, Cantürk Z, Baysal M, Asım Kaplancıklı, Z. Synthesis and evaluation of new thiazole derivatives as potential antimicrobial agents. Lett Drug Des Discov. 2016; 13(9):903-911.
[4] Grant EB, Guiadeen D, Baum EZ, Foleno BD, Jin H, Montenegro DA, Nelson EA, Bush K, Hlasta DJ. The synthesis and SAR of rhodanines as novel class C β-lactamase inhibitors. Bioorg Med Chem Lett. 2000; 10(19):2179-2182.
[5] Carlson EE, May JF, Kiessling LL. Chemical probes of UDP-galactopyranose mutase. Chem Biol. 2006; 13(8):825-837.
[6] Suree N, Yi SW, Thieu W, Marohn M, Damoiseaux R, Chan A, Jung ME, Clubb RT. Discovery and structure-activity relationship analysis of Staphylococcus aureus sortase A inhibitors. Bioorg Med Chem Lett. 2009; 17(20):7174-7185.
[7] Howard MH, Cenizal T, Gutteridge S, Hanna WS, Tao Y, Totrov M, Wittenbach VA, Zheng YJ. A novel class of inhibitors of peptide deformylase discovered through high-throughput screening and virtual ligand screening. J Med Chem. 2004; 47(27):6669-6672.
[8] Sim MM, Ng SB, Buss AD, Crasta SC, Goh KL, Lee SK. Benzylidene rhodanines as novel inhibitors of UDP-N-acetylmuramate/L-alanine ligase. Bioorg Med Chem Lett. 2002; 12(4):697-699.
[9] Zidar N, Tomašić T, Šink R, Rupnik V, Kovac A, Turk S, Patin D, Blanot D, Contreras Martel C, Dessen A, Müller Premru M, Zega A, Gobec S, Mašič LP, Kikelj D. Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD ligase. J Med Chem. 2010; 53(18):6584-6594.
[10] Kaminskyy D, Kryshchyshyn A, Lesyk R. Recent developments with rhodanine as a scaffold for drug discovery. Expert Opin Drug Discov. 2017; 12(12):1233-1252.
[11] Abu-Hashem AA, Abu-Zied KM, AbdelSalam Zaki ME, El-Shehry MF, Awad HM, Khedr MA. Design, synthesis, and anticancer potential of the enzyme (PARP-1) inhibitor with computational studies of new triazole, thiazolidinone,-thieno[2,3-d]pyrimidinones. Lett Drug Des Discov. 2020; 17(6):799-817.
[12] 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. Bioorg Chem. 2019; 86:126-36.
[13] Scarim CB, Jornada DH, Machado MG, Ferreira CM, dos Santos JL, Chung MC. Thiazole, thio and semicarba-zone derivatives against tropical infective diseases: Chagas disease, human African trypanosomiasis (HAT), leishmaniasis, and malaria. Eur J Med Chem. 2019; 162:378-95.
[14] Ilkiv II, Lesyk RB, Sklyarov OY. The influence of novel 4-thiazolidinone derivative es in cytoprotective mechanisms of small intestine under NSAID-induced damage. Ukr Biochem J. 2016: 88:99-104.
[15] 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.
[16] Lozynskyi A, Zasidko V, Atamanyuk D, Kaminskyy D, Derkach H, Karpenko O, Ogurtsov V, Kutsyk R, Lesyk R. Synthesis, antioxidant and antimicrobial activities of novel thiopyrano[2,3-d]thiazoles based on aroylacrylic acids. Mol Divers. 2017; 21(2):427-436.
[17] Güzeldemirci NU, Küçükbasmacı Ö. Synthesis and antimicrobial activity evaluation of new 1,2,4-triazoles and 1,3,4-thiadiazoles bearing imidazo[2,1-b]thiazole moiety. Eur J Med Chem. 2010; 45:63-68.
[18] Ur F, Cesur N, Birteksoez S, Oetuek G. Synthesis of some new 6-methylimid azo[2,1-b]thiazole-5-carbohydrazide derivatives and their antimicrobial activities. Arzneimittelforsch. 2004; 54(02):125-129.
[19] Bekhit AA, Fahmy HT, Rostom SA, Baraka AM. Design and synthesis of some substituted 1H-pyrazolyl-thiazolo[4,5-d]pyrimidines as anti-inflammatory-antimicrobial agents. Eur J Med Chem. 2003; 38:27-36.
[20] Gali R, Banothu J, Porika M, Velpula R, Hnamte S, Bavantula R, Abbagani S, Busi S. Indolylmethylene benzo[h]thiazolo[2,3-b]quinazolinones: Synthesis, characterization and evaluation of anticancer and antimicrobial activities. Bioorg Med Chem Lett. 2014; 24(17):4239-4242.
[21] Lin R, Johnson SG, Connolly PJ, Wetter SK, Binnun E, Hughes TV, Murray WV, Pandey NB, Moreno-Mazza SJ, Adams M, Fuentes-Pesquera AR. Synthesis and evaluation of 2,7-diamino-thiazolo[4,5-d]pyrimidine analogues as antitumor epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2009; 19(8):2333-2337.
[22] Walczyński K, Zuiderveld OP, Timmerman H. Non-imidazole histamine H3 ligands. Part III. New 4-n-propylpiperazines as non-imidazole histamine H3-antagonists. Eur J Med Chem. 2005; 40:15-23.
[23] Kulkarni SS, Newman AH. Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists. Bioorg Med Chem Lett. 2007; 17(11):2987-2991.
[24] Lee YR, Kim DJ, Mook-Jung I, Yoo KH. Synthesis of thia(oxa)zolopyridines and their inhibitory activities for β-amyloid fibrillization. Bull Korean Chem Soc. 2008; 29(12):2331-2336.
[25] Bebernitz GR, Beaulieu V, Dale BA, Deacon R, Duttaroy A, Gao J, Grondine MS, Gupta RC, Kakmak M, Kavana M, Kirman LC, Liang J, Maniara WM, Munshi S, Nadkarni SS, Schuster HF, Stams T, Denny ISt, Taslimi PM, Vash B, Caplan SL. Investigation of functionally liver selective glucokinase activators for the treatment of type 2 diabetes. J Med Chem. 2009; 52(19):6142-6152.
[26] Singh B, Bacon ER, Lesher GY, Robinson S, Pennock PO, Bode DC, Pagani ED, Bentley RG, Connell MJ, Hamel LT, Silver PJ. Novel and potent adenosine 3',5'-cyclic phosphatephosphodiesterase III inhibitors: thiazo-lo[4,5-b][1,6]naphthyridin-2-ones. J Med Chem. 1995; 38(14):2546-2550.
[27] Lozynskyi A, Zimenkovsky B, Ivasechko I, Senkiv J, Gzella A, Karpenko O, Stoika R, Lesyk R. Synthesis and cytotoxicity of new 2-oxo-7-phenyl-2,3-dihydrothiazolo[4,5-b]pyridine-5-carboxylic acid amides. Phosphorus Sulfur Silicon Relat Elem. 2019; 194(12):1149-1157.
[28] Lozynskyi A, Zimenkovsky B, Radko L, Stypula-Trebas S, Roman O, Gzella AK, Lesyk R. Synthesis and cytotoxicity 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):669-681.
[29] Matuschek E, Brown DF, Kahlmeter G. Development of the EUCAST disk diffusion antimicrobial susceptibility testing method and its implementation in routine microbiology laboratories. Clin Microbiol Infect. 2014; 20(4):O255-O266.
[30] Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012; 18(3):268-281.
[31] Thornsberry C, Mcdougal LK. Successful use of broth microdilution in susceptibility tests for methicillin-resistant (heteroresistant) staphylococci. J Clin Microbiol. 1983; 18(5):1084-1091.
[32] Holota SM, Derkach GO, Zasidko VV, Trokhymchuk VV, Furdychko LO, Demchuk IL, Semenciv GM, Soronovych II, Kutsyk RV, Lesyk RB. Antimicrobial activity of some 5-aminomethylene-2-thioxo-4-thiazolidinones. Biopolym Cell. 2019; 35(5):371-380.
[33] Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal. 2016; 6(2):71-79.
[34] Kim E, Lee SH, Lee SJ, Kwon OP, Yoon H. New antibacterial-core structures based on styryl quinolinium. Food Sci Biotechnol. 2017; 26(2):521-529.
[35] Patel HM, Bhardwaj V, Sharma P, Noolvi MN, Lohan S, Bansal S, Sharma A. Quinoxaline-PABA bipartite hy-brid derivatization approach: Design and search for antimicrobial agents. J Mol Struct. 2019; 1184:562-568.
[36] Hadda TB, Srivastava S, Das B, Salgado-Zamora H, Shaheen U, Bader A, Naseer MM. POM analyses of antimicrobial activity of some 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes: Favourable and unfavourable physico-chemical parameters in design of antibacterial and mycolytic agents. Med Chem Res. 2014; 23(2):995-1003.
[37] Hafez HN, Alsalamah SA, El-Gazzar AR. Synthesis of thiophene and N-substituted thieno[3,2-d]pyrimidine derivatives as potent antitumor and antibacterial agents. Acta Pharm. 2017; 67(3):275-292.
[38] Reheim MA, Baker SM. Synthesis, characterization and in vitro antimicrobial activity of novel fused pyrazo-lo[3,4-c]pyridazine, pyrazolo[3,4-d]pyrimidine, thieno[3,2-c]pyrazole and pyrazolo[3′,4′:4,5]thieno [2,3-d]pyrimidine derivatives. Chem Cent J. 2017; 11(1):112.