Biopolym. Cell. 2020; 36(5):381-391.
http://dx.doi.org/10.7124/bc.000A3A
Bioorganic Chemistry
Synthesis of indoline-thiazolidinone hybrids with antibacterial and antifungal activities
1Konechnyi Y. T., 1Lozynskyi A. V., 1Horishny V. Ya., 2Konechna R. T., 3Vynnytska R. B., 1Korniychuk O. P., 1, 4Lesyk R. B.
  1. Danylo Halytsky Lviv National Medical University
    69, Pekarska Str., Lviv, Ukraine, 79010
  2. Lviv Polytechnic National University
    12, S. Bandery Str., Lviv, Ukraine, 79013
  3. Ivano-Frankivsk National Medical Universitу
    2, Halytska Str., Ivano-Frankivsk, Ukraine, 76018
  4. University of Information Technology and Management in Rzeszow
    2, Sucharskiego Str., Rzeszow, Poland, 35-225

Abstract

Aim. Based of the Knoevenagel condensation reaction the synthesis of new rhodanine-indoline hybrid molecules for screening antibacterial and antifungal activities was accomplished. Methods. Organic synthesis, NMR spectroscopy, pharmacological screening. Results. The reaction between rhodanine-3-propanoic/ethanesulfonic acids and indolecarbaldehydes in the acetic acid medium providing series of 5-indolylmethylenerhodanine-3-carboxylic/sulfonic acid derivatives. Based on the esterification reaction with methanol in the presence of sulfuric acid, 5-indolylmethylenerhodanine-3-propanic acid was transformed into appropriate ester for further evaluation of antimicrobial activity. The antimicrobial activity screening allowed the identification of compounds with significant effect against Escherichia coli, Staphylococcus lentus and Candida albicans with [the] MIC/MBC/MFC values in the range of 25-50 μg/mL. Conclusions. The synthesized 5-indolylmethylenerhodanine-3-carboxylic/sulfonic acid derivatives are a convenient platform for the development of new highly active and low-toxic agents as potential drug-like molecules with antimicrobial activity.
Keywords: synthesis, 2-thioxo-4-thiazolidinone, indolecarbaldehydes, spectral data, antimicrobial activity
Full text: (PDF, in English)

References

[1] Mendelson M, Matsoso MP. The World Health Organization Global Action Plan for antimicrobial resistance. S Afr Med J. 2015;105(5):325.
[2] Piggott AM, Karuso P. Quality, not quantity: the role of natural products and chemical proteomics in modern drug discovery. Comb Chem High Throughput Screen. 2004;7(7):607-30.
[3] 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.
[4] Tripathi AC, Gupta SJ, Fatima GN, Sonar PK, Verma A, Saraf SK. 4-Thiazolidinones: the advances continue…. Eur J Med Chem. 2014;72:52-77.
[5] Mendgen T, Steuer C, Klein CD. Privileged scaffolds or promiscuous binders: a comparative study on rhodanines and related heterocycles in medicinal chemistry. J Med Chem. 2012;55(2):743-53.
[6] Kryshchyshyn A, Kaminskyy D, Grellier P, Lesyk R. Trends in research of antitrypanosomal agents among synthetic heterocycles. Eur J Med Chem. 2014;85:51-64.
[7] el-Sabbagh OI, Baraka MM, Ibrahim SM, Pannecouque C, Andrei G, Snoeck R, Balzarini J, Rashad AA. Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur J Med Chem. 2009;44(9):3746-53.
[8] de Souza MV. Synthesis and biological activity of natural thiazoles: An important class of heterocyclic compounds. J Sulfur Chem. 2005; 26(4-5):429–49.
[9] Wang S, Zhao Y, Zhu W, Liu Y, Guo K, Gong P. Synthesis and anticancer activity of Indolin-2-one derivatives bearing the 4-thiazolidinone moiety. Arch Pharm (Weinheim). 2012;345(1):73-80.
[10] Verma A, Saraf SK. 4-thiazolidinone--a biologically active scaffold. Eur J Med Chem. 2008;43(5):897-905.
[11] Lozynskyi A, Zimenkovsky B, Radko L, Stypula-Trebas S, Roman O, Gzella AK, Lesyk R. Synthesis and cyto-toxicity of new thiazolo[4,5-b]pyridine-2(3H)-one derivatives based on α,β-unsaturated ketones and α-ketoacids. Chem Pap. 2018; 72:669–81.
[12] 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.
[13] Geronikaki AA, Pitta EP, Liaras KS. Thiazoles and thiazolidinones as antioxidants. Curr Med Chem. 2013;20(36):4460-80.
[14] Fomenko I, Bondarchuk T, Emelyanenko V, Denysenko N, Pavlo S, Ilkiv I, Lesyk R, Sklyarov A. Changes of nitric oxide system and lipid peroxidation parameters in the digestive system of rats under conditions of acute stress, and use of nonsteroidal anti-inflammatory drugs. Curr Issues Pharm Med. Sci. 2015; 28(1):37–41.
[15] Ilkiv I, Lesyk R, Sklyarov O. Evaluation of novel 4-thiazolidinone-based derivatives as possible cytoprotective agents against stress model in rats. J Appl Pharm Sci. 2017; 7:199–203.
[16] Ottanà R, Maccari R, Barreca ML, Bruno G, Rotondo A, Rossi A, Chiricosta G, Di Paola R, Sautebin L, Cuzzocrea S, Vigorita MG. 5-Arylidene-2-imino-4-thiazolidinones: design and synthesis of novel anti-inflammatory agents. Bioorg Med Chem. 2005;13(13):4243-52.
[17] Horishny V, Kartsev V, Geronikaki A, Matiychuk V, Petrou A, Glamoclija J, Ciric A, Sokovic M. 5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies. Molecules. 2020;25(8):1964.
[18] Vicini P, Geronikaki A, Anastasia K, Incerti M, Zani F. Synthesis and antimicrobial activity of novel 2-thiazolylimino-5-arylidene-4-thiazolidinones. Bioorg Med Chem. 2006;14(11):3859-64.
[19] 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 beta-lactamase inhibitors. Bioorg Med Chem Lett. 2000;10(19):2179-82.
[20] 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. 2009;17(20):7174-85.
[21] 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):6669-72.
[22] Carlson EE, May JF, Kiessling LL. Chemical probes of UDP-galactopyranose mutase. Chem Biol. 2006;13(8):825-37.
[23] 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):697-9.
[24] Smith TK, Young BL, Denton H, Hughes DL, Wagner GK. First small molecular inhibitors of T. brucei dolicholphosphate mannose synthase (DPMS), a validated drug target in African sleeping sickness. Bioorg Med Chem Lett. 2009;19(6):1749-52.
[25] Havrylyuk D, Zimenkovsky B, Lesyk R. Synthesis, biological activity of thiazolidinones bearing indoline moiety and isatin based hybrids. Mini-Rev Org Chem. 2015; 12(1):66–87.
[26] Kende H, Zeevaart J. The Five "Classical" Plant Hormones. Plant Cell. 1997;9(7):1197-1210.
[27] de Sá Alves FR, Barreiro EJ, Fraga CA. From nature to drug discovery: the indole scaffold as a 'privileged structure'. Mini Rev Med Chem. 2009;9(7):782-93.
[28] Chadha N, Silakari O. Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view. Eur J Med Chem. 2017;134:159-184.
[29] Olgen S, Ozkan S. A study of 3-substituted benzylidene-1,3-dihydro-indoline derivatives as antimicrobial and antiviral agents. Z Naturforsch C J Biosci. 2009;64(3-4):155-62.
[30] Farag AA. Synthesis and Antimicrobial Activity of 5-(morpholinosulfonyl)isatin Derivatives Incorporating a Thiazole Moiety. Drug Res (Stuttg). 2015;65(7):373-9.
[31] Tejchman W, Korona-Glowniak I, Malm A, Zylewski M, Suder P. Antibacterial properties of 5-substituted derivatives of rhodanine-3-carboxyalkyl acids. Med Chem Res. 2017;26(6):1316-1324.
[32] 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):O255-66.
[33] Chowdhary A, Singh PK, Kathuria S, Hagen F, Meis JF. Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species. Antimicrob Agents Chemother. 2015;59(12):7882-7.
[34] Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: A review. J Pharm Anal. 2016;6(2):71-79.
[35] Litchfield JT Jr, Wilcoxon F. A simplified method of evaluating dose-effect experiments. J Pharmacol Exp Ther. 1949;96(2):99-113.
[36] Smith WG. 1 pharmacological screening tests. Prog Med Chem. 1961; 1:1–33.
[37] 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):268-81.