2-(4-Oxo-1,3-thiazolidin-2-ylidene)acetamid as promising scaffold for designing new antifungal compounds published by Ural Federal University eISSN 2411-1414 chimicatechnoacta.ru LETTER 2023, vol. 10(1), No. 202310106 DOI: 10.15826/chimtech.2023.10.1.06 1 of 5 2-(4-Oxo-1,3-thiazolidin-2-ylidene)acetamid as promising scaffold for designing new antifungal compounds Konstantin L. Obydennov * , Tatiana A. Kalinina , Daria V. Ryabova, Maria F. Kosterina, Tatiana V. Glukhareva Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620009, Russia * Corresponding author: k.l.obydennov@urfu.ru This paper belongs to the MOSM2022 Special Issue. Abstract 1,3-Thiazolidin-4-one derivatives with an exocyclic C=C double bond in po- sition 2 of the hetero ring have a wide spectrum of biological activity, but their fungicidal activity has not been studied as much as it should be. This paper presents a simple and convenient approach for obtaining potential antifungal agents based on 2-(4-oxo-1,3-thiazolidin-2-ylidene)acetamides. The first examples of evaluating the fungicidal activity of 8 obtained com- pounds on 8 strains of phytopathogenic fungi are presented. A highly ac- tive compound 4e with EC50 of 0.85 and 2.29 µg/mL against A. solani and P. lingam, respectively, was found to be promising for further study. Keywords 1,3-thiazolidine cyanoacetamide exocyclic double bond fungicide biological activity Received: 08.12.22 Revised: 21.12.22 Accepted: 22.12.22 Available online: 29.12.22 © 2022, the Authors. This article is published in open access under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 1. Introduction Derivatives of 1,3-thiazolidin-4-one with a double C=O, C=N, C=S, C=C exocyclic bond in position 2 of the hetero ring have a wide range of biological activity: antituberculo- sis [1], antioxidant [2], anticancer [3, 4], antiinflammatory [5], anticonvulsant [6], antiviral [7, 8], trypanocidal [9], antiarrhythmic [10], antibacterial [11, 12] and fungicidal [12, 13]. Although 1,3-thiazolidines and 1,3-thiazolines have centers for polar interactions and hydrogen bonds [14], these heterocycles often act as a scaffold for substituents interacting with biotargets. Thus, the analysis of the crystal structure of the complex of succinate dehydrogenase with the inhibitor thiapronil I (pdb id: 6MYR) showed that thiapronil I does not form strong non-covalent interactions (hydrogen bonds and π–π interactions) with the enzyme due to the 1,3-thiazol-2-ylidene fragment [15]. Anticancer compounds II [16] and III [17] containing a 3,4,5-tri- methoxyphenyl substituent are prominent examples as well. Due to this substituting group, compounds II and III bind to the bioreceptor tubulin (Scheme 1) [18]. It is known that 1,3-thiazolidine derivatives with C=O [2, 19], C=N [20–22], C=S [23] exocyclic bonds in position 2 of the hetero ring show fungicidal properties. However, information on the study of the antifungal properties of 1,3- thiazolidine with a C=C double bond in position 2 of the ring is limited [12]. For example, 1,3-thiazolindin-2-ylidene IV is known to exhibit antifungal activity against human patho- gens C. albicans and C. neoformans [24]. One of the convenient methods for the synthesis of 1,3- thiazolidin-2-ylidene derivatives is the condensation of cy- anoacetamides 1 with thioglycolic acid 2 (Scheme 2) [25]. In this case, 1,3-thiazolidin-2-ylidenes 3 can be modified both at the NH and CH2 groups of the hetero ring. Scheme 1 Examples of active 1,3-thiazol-2-ylidene and 1,3-thiazol- idin-2-ylidene derivatives. http://chimicatechnoacta.ru/ https://doi.org/10.15826/chimtech.2023.10.1.06 http://creativecommons.org/licenses/by/4.0/ https://orcid.org/0000-0002-5884-4105 https://orcid.org/0000-0002-7549-686X https://orcid.org/0000-0002-5231-9879 https://crossmark.crossref.org/dialog/?doi=https://doi.org/10.15826/chimtech.2023.10.1.06&domain=pdf&date_stamp=2022-12-29 https://journals.urfu.ru/index.php/chimtech/rt/suppFiles/6411/0 Chimica Techno Acta 2023, vol. 10(1), No. 202310106 LETTER 2 of 5 DOI: 10.15826/chimtech.2023.10.1.06 Scheme 2 Synthesis of 1,3-thiazolidin-2-ylidenes. As a result of varying the substituents in the acetamide fragment and the hetero ring, a wide range of 1,3-thiazoli- din-2-ylidenes can be obtained for the search for biologi- cally active compounds. In this paper, we present the first results of using this approach to search for antifungal compounds. 2. Experimental 2.1. Synthesis of target compounds 1H and 13C NMR spectra were recorded with a Bruker Avance II (Karlsruhe, Germany) spectrometer (400 MHz for 1H, 100 MHz for 13C) using Me4Si as an internal standard. The NMR spectra of all compounds are demonstrated in the Supporting Information (Figures S1–S10). Mass spectra were recorded with a Shimadzu GCMS-QP 2010 “Ultra” (Kyoto, Japan) in electron ionization (EI) mode (electron energy 70 eV). The Fourier transform infrared (FT-IR) spec- tra were obtained using a Bruker Alpha (ATR, ZnSe) spec- trometer (Ettlingen, Germany). Elemental analyses were performed with a Perkin-Elmer 2400 Series II CHNS/O an- alyzer (Shelton, CT USA). Melting points were determined using a Stuart SMP 3 apparatus (Staffordshire, ST15 OSA, UK). The progress of the reactions and the purity of the compounds were monitored by thin-layer chromatography (TLC, Merck KGaA) in an ethyl acetate-hexane system. The synthesis of compounds 3a–c was carried out ac- cording to the published method [25]. Alkylation reaction of thiazolidines 3a–c with the for- mation of products 4a–e was carried out according to the published method [26]. (2Z)-N-benzyl-2-(4-oxo-1,3-thiazolidin-2-ylidene)ac- etamide (3a). Yield 0.37 g (72%), white powder, mp 207– 209 °С (lit. 208–209 °С [25]). (2Z)-2-(4-oxo-1,3-thiazolidin-2-ylidene)-N-phenyla- cetamide (3b). Yield 0.44 g (67%), white powder, mp 290– 293 °С (decomp.) (lit. 282–285 °C [25]). (2Z)-N-(2-methylphenyl)-2-(4-oxo-1,3-thiazolidin-2- ylidene)acetamide (3c). Yield 0.23 g (75%), white powder, mp 235–236 °С. IR spectrum, ν, cm–1: 3205 (NH), 2969, 2594, 1702 (C=O), 1623 (C=O), 1600, 1576, 1549, 1492, 1456, 1427, 1399, 1367, 1319. 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm, (J, Hz): 2.19 (3H, s, CH3); 3.67 (2H, s, CH2); 5.91 (1H, s, CH=); 7.02 (1H, t, J = 7.2, Ar H); 7.00 (1H, t, J = 7.3, Ph p-H); 7.08–7.24 (2H, m, Ph H); 7.49 (1H, d, J = 7.4, Ph H); 9.08 (1H, s, NH); 11.46 (1H, s, NH). 13С NMR spectrum (100 MHz, DMSO-d6, δ, ppm: 17.99 (CH3); 32.00 (CH2); 92.37 (С-2’); 124.36 (2C Ar); 125.78 (C Ar); 130.18 (C Ar); 130.77 (C Ar); 136.79 (C Ar), 153.92 (С-2); 165.40 (C=O), 174.18 (C=O). Found, %: C 58.05; H 4.87; N 11.28. C12H12N2O2S. Calculated, %: C 57.96; H 4.66; N 11.36. (2Z)-N-benzyl-2-(3-methyl-4-oxo-1,3-thiazolidin-2- ylidene)acetamide (4a). Yield 0.50 g (64%), white pow- der, mp 183–186 °С. IR spectrum, ν, cm–1: 3295 (NH), 1705 (C=O), 1635 (C=O), 1623, 1553, 1534, 1495, 1453, 1431, 1411, 1386, 1334. 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm, (J, Hz): 3.04 (3H, s, CH3); 3.72 (2H, s, CH2); 4.32 (2H, d, J = 5.4, CH2N); 5.67 (1H, s, CH=); 7.22–7.34 (5H, m, Ph H); 8.22 (1H, t, J = 5.1, NH). 13С NMR spectrum (100 MHz, DMSO-d6, δ, ppm: 29.47 (CH2); 31.10 (CH3); 93.13 (С- 2’); 126.70 (C Ar); 127.24 (C Ar); 128.25 (C Ar); 139.81 (C Ar); 153.08 (C-2), 166.19 (C=O), 172.12 (C=O). EI-MS m/z (%): 262 [М]+ (90). Found, %: C 59.52; H 5.38; N 10.68. C13H14N2O2S. Calculated, %: C 59.32; H 5.37; N 10.56. (2Z)-N-benzyl-2-(3-benzyl-4-oxo-1,3-thiazolidin-2- ylidene)acetamide (4b). Yield 0.31 g (76%), white pow- der, mp 144-147 °С. IR spectrum, ν, cm–1: 3307 (NH), 1720 (C=O), 1649 (C=O), 1631, 1572, 1546, 1495, 1454, 1430, 1389, 1364, 1321. 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm, (J, Hz): 3.86 (2H, s, CH2); 4.25 (2H, d, J = 5.5, CH2N); 4.79 (2H, s, CH2N); 5.65 (1H, s, CH=); 7.21– 7.37 (10H, m, Ph H); 8.17 (1H, t, J = 5.2, NH). 13С NMR spec- trum (100 MHz, DMSO-d6, δ, ppm: 31.45 (CH2); 42.49 (CH2N); 46.38 (CH2N); 94.32 (С-2’); 127.26 (C Ar); 127.90 (C Ar); 127.97 (C Ar); 128.75 (C Ar); 129.11 (C Ar); 135.56 (C Ar); 140.15 (C Ar); 152.47 (C-2), 166.53 (C=O), 173.21 (C=O). EI-MS m/z (%): 338 [М]+ (23.79). Found, %: C 67.43; H 5.36; N 8.28. C19H18N2O2S. Calculated, %: C 67.38; H 5.35; N 8.41. (2Z)-2-(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene)-N- phenylacetamide (4c). Yield 0.22 g (79%), white powder, mp 209–211 °C (lit. 205–208 °C [26,27]). IR spectrum, ν, cm–1: 3447 (NH), 1714 (C=O), 1650 (C=O), 1617, 1608, 1596, 1567, 1494, 1443, 1421, 1405, 1346, 13.11. 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm, (J, Hz): 3.09 (3H, s, CH3); 3.78 (2H, s, CH2); 5.80 (1H, s, CH=); 7.00 (1H, t, J = 7.3, Ph p-H); 7.28 (2H, t, J = 7.7, Ph H); 7.60 (2H, t, J = 7.9, Ph H); 9.87 (1H, s, NH). 13С NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 29.43 (CH3); 31.00 (CH3); 93.37 (С-2’); 118.50 (C Ar); 122.38 (C Ar); 128.45 (C Ar); 139.49 (C Ar); 154.76 (C- 2), 164.79 (C=O), 171.95 (C=O). EI-MS m/z (%): 248 [М]+ (31). Found, %: C 58.05; H 4.87; N 11.28. C12H12N2O2S. Cal- culated, %: C 58.27; H 5.07; N 11.45. (2Z)-2-(3-benzyl-4-oxo-1,3-thiazolidin-2-ylidene)-N- phenylacetamide (4d). Yield 0.54 g (80%), white powder, mp 214–217 °C (lit. 216–218 °C [27]). (2Z)-2-(3-benzyl-4-oxo-1,3-thiazolidin-2-ylidene)-N- (2-methylphenyl)acetamide (4e). Yield 0.37 g (76%), white powder, mp 166–169 °C. IR spectrum, ν, cm–1: 3274.81, 3062.51, 1713.51 (C=O), 1653.91 (C=O), 1639.00, 1578.96, 1566.82, 1535.97, 1494.73, 1455.75, 1397.69, 1364.59, 1316.31. 1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm, (J, Hz): 2.16 (3H, s, CH3); 3.90 (2H, s, CH2); 4.85 (2H, s, CH2N); 5.96 (1H, s, CH=); 7.02–7.48 (9H, m, Ar H); 9.06 (1H, s, NH). 13С NMR spectrum (100 MHz, DMSO-d6), δ, ppm: 17.93 (CH3); https://doi.org/10.15826/chimtech.2023.10.1.06 https://doi.org/10.15826/chimtech.2023.10.1.06 Chimica Techno Acta 2023, vol. 10(1), No. 202310106 LETTER 3 of 5 DOI: 10.15826/chimtech.2023.10.1.06 31.02 (CH2); 45.98 (CH2N); 93.81 (С-2’); 124.08 (C Ar); 124.42 (C Ar); 125.84 (C Ar); 126.72 (C Ar); 127.51 (C Ar); 128.66 (C Ar); 130.22 (C Ar); 130.41 (C Ar); 135.04 (C Ar); 136.53 (C Ar); 153.86 (C-2); 165.00 (C=O); 172.78 (C=O). EI-MS m/z (%): 338 [М]+ (8.83). Found, %: С 67.43; H 5.36; N 8.28. C19H18N2O2S. Calculated, %: C 67.58; H 5.20; N 8.19. 2.2. Study of fungicidal activity The fungicidal activity of compounds 3a–c and 4a–e was tested in vitro on Alternaria solani Sorauer MFP601021, Bo- trytis cinerea Pers. MFG 60449, Colletotrichum coccodes JS 161-1, Fusarium solani (Mart.) Sacc. MFG 70523, Phy- tophthora infestans (Mont.) de Bary, Plenodomus lingam (Tode:Fr.) Höhn. MF Br17-044, Rhizoctonia solani RCAM01785 and Sclerotinia sclerotiorum using the agar block method. P. infestans was isolated at Nankai Univer- sity (Tianjin, China). C. coccodes was purchased from the All-Russian Collection of Industrial Microorganisms (Mos- cow, Russia). The remaining strains of fungi were pur- chased from the Russian Collection of Agricultural Microor- ganisms (St. Petersburg, Russia). Solutions of the tested compounds were prepared at a concentration of 0.5 mg/mL by dissolving 5 mg of the com- pound in 1 mL of DMSO with the addition of 9 mL of water. A total 1 mL of the test solutions was added to sterile Petri dishes containing 9 mL of heated (60 °C) nutrient medium and then mixed in a laminar flow cabinet. Fungal discs (4 mm in diameter) were cup under aseptic conditions from a 7-day-old culture of the test fungus using a sterile cork borer. The mycelium discs were placed in the center of Petri dishes containing the culture medium at room temperature. A negative control was prepared with the culture medium and DMSO. The fungi were incubated at 25 °С (48 h for R. solani, 120 h for A. solani, P. lingam, 72 h for other fungi). After incubation, the diameter of fungal colonies was meas- ured. The percentage of fungus growth inhibition was de- termined by the formula [28]: I (%) = [(C – T)/(C – 4 mm)]·100, (1) where I (%) – the degree of inhibition of mycelial growth, Т (mm) – the mean value of the diameter of the colonies in the presence of a given concentration of each compound, and С (mm) – the mean diameter of the colonies in the ab- sence of the compound under the same conditions. All the experiments were carried out in triplicate. The standard de- viation was calculated. The half maximal effective concentration for compound 4e was determined by linear regression of the probability of the corresponding percentage of fungus radial growth from the logarithm of the concentration [29] in the GraphPad Prism 9.4.1 program. The commercial fungicide carbendazim, which is highly active against P. lingam, was used as a comparator agent. 3. Results and Discussion Compounds 3а–с were obtained by reacting the correspond- ing cyanoacetamides 1a–c with thioglycolic acid 2 in pyri- dine with the addition of dimethylaminopyridine as a cata- lyst according to a previously published procedure (Scheme 3 [25]. Further alkylation with methyl iodide or benzyl chlo- ride in dimethylformamide in the presence of K2CO3 gave products 4a–e in 64–80% yields. The fungicidal activity of obtained compounds 3a–c and 4a–e was studied against 8 strains of phytopathogenic fungi that are widespread and cause significant damage to agriculture, such as A. solani, B. cinerea, C. coccodes, F. solani, P. infestans, P. lingam, R. solani and S. sclerotiorum. An in vitro study of antifungal activity showed that most of the obtained compounds exhibit low (I  50%) or mod- erate (50%  I  70%) activity against phytopathogenic fungi, inhibiting the growth of mycelium by 65% or less (Table 1). However, compound 4e, containing 2-methylphenyl at the nitrogen atom of the acetamide fragment and benzyl at the nitrogen atom of the thiazolidine ring, showed high ac- tivity against A. solani (causative agent of early blight of nightshade crops) and P. lingam (causative agent of crucif- erous plants phomosis) with the inhibition degree of the fungi radial growth 75.77 and 85.94%, respectively. Scheme 3 Synthesis of compounds 3а–с and 4a–e. Table 1 Results of antifungal activity study in vitro for compounds 3a–c and 4a–e at a concentration of 50 μg/mL*. Com- pounds Degree of inhibition of mycelial growth (I±SD, %) A. solani B. cinerea C. coccodes F. solani R. solani P. infestans P. lingam S. scleroti- orum 3a 29.60±0.53 29.95±0.96 9.34±0.65 7.28±1.17 13.38±0.72 8.77±0.35 28.95±2.26 31.58±0.31 3b 37.80±0.60 32.50±1.21 4.20±0.77 9.63±0.99 9.75±0.68 5.48±0.60 1.95±0.16 6.06±0.94 3c 54.95±2.02 6.70±0.23 39.21±0.22 4.86±0.63 2.40±0.79 6.33±0.50 26.12±3.30 10.98±3.11 4a 37.22±2.63 12.25±0.67 58.65±0.18 1.08±1.12 9.76±0.77 10.25±0.21 43.45±2.48 17.01±1.04 4b 54.11±0.61 10.84±2.19 36.18±1.04 5.09±0.28 9.59±0.18 9.90±0.88 31.83±0.63 25.63±0.34 4c 51.73±1.56 8.21±0.76 47.04±0.52 3.42±0.38 0 12.33±1.12 30.59±1.15 64.45±2.10 4d 47.37±0.47 7.92±0.61 19.43±0.57 6.83±0.66 9.84±0.81 8.62±0.91 11.83±0.34 7.58±1.71 4e 75.77±0.39 22.89±1.00 54.47±0.11 8.74±0.96 3.27±0.32 10.23±1.38 85.94±0.06 34.09±0.91 *SD – standard deviation, I = 100 – active compound, I = 0 – in active compound. https://doi.org/10.15826/chimtech.2023.10.1.06 https://doi.org/10.15826/chimtech.2023.10.1.06 Chimica Techno Acta 2023, vol. 10(1), No. 202310106 LETTER 4 of 5 DOI: 10.15826/chimtech.2023.10.1.06 Half maximal effective concentration values of 1,3-thia- zolidin-2-ylidene 4e for A. solani and P. lingam were deter- mined (Table 2). Thus, promising results were obtained. Compound 4e was found to have low EC50 values at the level of 1–2 μg/mL, comparable with commercial fungicides [30]. 4. Limitations In this paper, we present the first data on the antifungal activity of 2-(4-oxo-1,3-thiazolidin-2-ylidene)acetamide de- rivatives. The proposed approach for the preparation of po- tential fungicides is a one-step method for the synthesis of 2-(4-oxo-1,3-thiazolidin-2-ylidene)acetamide scaffold. This approachmakes it easy to modify the resulting compounds. Using this strategy makes it possible to obtain a wide range of compounds. Thus, this direction in the future will be fol- lowed so as to discover new compounds that are highly ac- tive against fungi. For targeted design of the potential fun- gicide structures based on the 2-(4-oxo-1,3-thiazolidin-2- ylidene)acetamides, additional studies of the mode of their biological action and identification of biological targets are required. Also, it is necessary to perform further biological studies in vivo of the highly active compounds to evaluate their se- lectivity, toxicity to humans, animals and beneficial micro- organisms, etc. 5. Conclusions Thus, as a result of the work, we synthesized 8 derivatives of 2-(4-oxo-1,3-thiazolidin-2-ylidene)acetamide and studied their fungicidal activity in vitro. Compound 4e was highly ac- tive against A. solani and P. lingam. It was shown that 2-(4- oxo-1,3-thiazolidin-2-ylidene)acetamides are promising base compounds for designing new fungicides. ● Supplementary materials This article contains supplementary materials with copies of 1H, and 13C spectra, which are available on the corre- sponding online page. ● Funding This research was supported by the Russian Science Foun- dation and Government of Sverdlovsk region, Joint Grant No 22-26-20124, https://rscf.ru/en/project/22-26-20124. ● Acknowledgments The authors are grateful to the Laboratory of Integrated Re- search and Expert Evaluation of Organic Materials of Ural Federal University for the registration of NMR spectra of compounds. Table 2 Antifungal EC50 values of compound 4e. Fungi Com- pounds Regression equation R2 EC50, μg/mL A. solani 4e y = 1.4767x+9.5355 0.9654 0.85 CZ* y = 0.5110x+2.3270 0.9794 >10000 P. lingam 4e y = 2.3053x+11.0900 0.9881 2.29 CZ y = 3.649x+15.7200 0.9880 1.15 *CZ – commercial fungicide carbendazim. ● Author contributions Conceptualization: К.L.O., T.V.G. Data curation: K.L.O., T.A.K. Formal Analysis: T.A.K. Funding acquisition: T.A.K. Investigation: T.A.K., D.V.R., M.F.K. Methodology: T.V.G., K.L.O. Project administration: T.A.K. Resources: T.A.K., T.V.G. Supervision: T.V.G. Validation: T.A.K., T.V.G. Visualization: K.L.O. Writing – original draft: K.L.O., T.A.K. Writing – review & editing: T.V.G. ● Conflict of interest The authors declare no conflict of interest. ● Additional information Author IDs: Konstantin L. Obydennov, Scopus ID 54684683000; Tatiana A. Kalinina, Scopus ID 54684032600; Maria F. Kosterina, Scopus ID 6506644209; Tatiana V. Glukhareva, Scopus ID 6602582999. Website: Ural Federal University, https://urfu.ru/en. References 1. Trotsko N. Antitubercular properties of thiazolidin-4-oneseA review. Eur J Med Chem. 2021;215:113266. doi:10.1016/j.ejmech.2021.113266 2. Kumar H, Deep A, Kumar Marwaha R. Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(sub- stituted aryl/alkyl)methyl)benzylidene)thiazolidine-2,4-dione derivatives. BMC Chem. 2020;14:25. doi:10.1186/s13065-020-00678-2 3. Chandrappa S, Kavitha CV, Shahabuddin MS, Vinaya K, Ananda Kumar CS, Ranganatha SR, Raghavan SC, Rangappa KS. Synthesis of 2-(5-((5-(4-chlorophenyl)furan-2-yl)meth- ylene)-4-oxo-2-thioxothiazolidin-3-yl)acetic acid derivatives and evaluation of their cytotoxicity and induction of apopto- sis in human leukemia cells. Bioorg Med Chem. 2009;17(6):2576–2584. doi:10.1016/j.bmc.2009.01.016 4. 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, cytose- lective toxicity, structure-activity relationships, and pharma- cophore of thiazolidinone derivatives targeting drug-resistant https://doi.org/10.15826/chimtech.2023.10.1.06 https://doi.org/10.15826/chimtech.2023.10.1.06 https://rscf.ru/en/project/22-26-20124 https://www.scopus.com/authid/detail.uri?authorId=54684683000 https://www.scopus.com/authid/detail.uri?authorId=54684032600 https://www.scopus.com/authid/detail.uri?authorId=6506644209 https://www.scopus.com/authid/detail.uri?authorId=6602582999 https://urfu.ru/en https://doi.org/10.1016/j.ejmech.2021.113266 https://doi.org/10.1186/s13065-020-00678-2 https://doi.org/10.1016/j.bmc.2009.01.016 Chimica Techno Acta 2023, vol. 10(1), No. 202310106 LETTER 5 of 5 DOI: 10.15826/chimtech.2023.10.1.06 lung cancer cells. J Med Chem. 2008;51(5):1242–1251. doi:10.1021/jm7012024 5. Uchôa FDT, da Silva TG, de Lima M do CA, Galdino SL, Pitta I da R, Costa TD. Preclinical pharmacokinetic and pharmacody- namic evaluation of thiazolidinone PG15: An anti-inflamma- tory candidate. J Pharm Pharmacol. 2009;61(3):339–345. doi:10.1211/jpp.61.03.0008 6. Agarwal A, Lata S, Saxena KK, Srivastava VK, Kumar A. Syn- thesis and anticonvulsant activity of some potential thiazoli- dinonyl 2-oxo/thiobarbituric acids. Eur J Med Chem. 2006;41(10): 1223–1229. doi:10.1016/j.ejmech.2006.03.029 7. Terzioğlu N, Karalı N, Gürsoy A, Pannecouque C, Leysen P, Paeshuyse J, Neyts J, De Clercq E. Synthesis and primary anti- viral activity evaluation of 3-hydrazono-5-nitro-2-indolinone derivatives. Arkivoc. 2006;1:109–118. 8. Powers JP, Piper DE, Li Y, Mayorga V, Anzola J, Chen JM, Jaen JC, Lee G, Liu J, Peterson MG, Tonn GR, Ye Q, Walker PC, Wang, Z. SAR and Mode of Action of Novel Non-Nucleoside Inhibitors of Hepatitis C NS5b RNA Polymerase. J Med Chem. 2006;49:1034–1046. doi:10.1021/jm050859x 9. Pizzo C, Saiz C, Talevi A, Gavernet L, Palestro P, Bellera C, Cazzulo JJ, Chidichimo A, Wipf P, Mahler SG. Synthesis of 2- Hydrazolyl-4-Thiazolidinones Based on Multicomponent Re- actions and Biological Evaluation Against Trypanosoma Cruzi. Chem Biol Drug Des. 2011;77(3):166–172. doi:10.1111/j.1747-0285.2010.01071.x 10. Bhandari SV, Bothara KG, Patil AA, Chitre TS, Sarkate AP, Gore ST, Dangre SC, Khachane CV. Design, Synthesis and Pharmacological Screening of Novel Antihypertensive Agents Using Hybrid Approach. Bioorg Med Chem. 2009;17(1),390– 400. doi:10.1016/j.bmc.2008.10.032 11. Vicini P, Geronikaki A, Incerti M, Zani F, Dearden J, Hewitt M. 2-Heteroarylimino-5-benzylidene-4-thiazolidinones ana- logues of 2-thiazolylimino-5-benzylidene-4-thiazolidinones with antimicrobial activity: Synthesis and structure-activity relationship. Bioorg Med Chem. 2008;16(7):3714–3724. doi:10.1016/j.bmc.2008.02.001 12. Salem MA. Synthesis of New Thiazole, Bithiazolidinone and Pyrano[2,3-d]thiazole Derivatives as Potential Antimicrobial Agents. Croat Chem Acta. 2017;90(1):7–15. doi:10.5562/cca2955 13. Siddiqui IR, Singh PK, Singh J, Singh J. Facile synthesis and fungicidal activity of novel 4,4'-bis[2''-(5'''-substituted rhodanin-3'''-yl)thiazol-4"-yl]bibenzyls. Indian J. Chem., Sect B [Internet]. 2005[cited 2016];44: 2102–6. English. Available from: http://nopr.niscpr.res.in/handle/123456789/9197, Ac- cessed on 07 December 2022. 14. Mendgen T, Steuer C, Klein CD. Privileged scaffolds or pro- miscuous binders: A comparative study on rhodanines and related heterocycles in medicinal chemistry. J Med Chem. 2011;55(2):743–753. doi:10.1021/jm201243p 15. Huang L, Lümmen P, Berry EA. Crystallographic investigation of the ubiquinone binding site of respiratory Complex II and its inhibitors. Biochim Biophys Acta – Proteins and Proteom. 2021;1869:140679. doi:10.1016/j.bbapap 16. Noha RM, El hamid MK, Ismail MM, Manal RM, Salwa E. De- sign, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic mol- ecules on (HCT-116) colon cancer cells. Eur J Med Chem. 2091:112870. doi:10.1016/j.ejmech.2020.112870 17. 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 Chem Life Sci. 2012;345:73–80. doi:10.1002/ardp.201100082 18. Ranjan P, Kumar SP, Kari V, Jha PC. Exploration of interac- tion zones of b-tubulin colchicine binding domain of hel- minths and binding mechanism of anthelmintics. Comput Biol Chem. 2017;68:78–91. doi:10.1016/j.compbiolchem.2017.02.008 19. Avupati VR, Yejella RP, Akula A, Guntuku GS, Doddi BR, Vutla VR, Anagani SR, Adimulam LS, Vyricharla AK. Synthesis, characterization and biological evaluation of some novel 2,4- thiazolidinediones as potential cytotoxic, antimicrobial and antihyperglycemic agents. Bioorg Med Chem Lett. 2012;22(20):6442–6450. doi:10.1016/j.bmcl.2012.08.052 20. Li YX, Wang SH, Li ZM, Su N, Zhao WG. Synthesis of novel 2- phenylsulfonylhydrazono-3-(2′,3′,4′,6′-tetra-O-acetyl-β-d-glu- copyranosyl)thiazolidine-4-ones from thiosemicarbazide pre- cursors. Carbohydr Res. 2006;341(17):2867–2870. doi:10.1016/j.carres.2006.09.010 21. Haroun M, Tratrat C, Kolokotroni A, Petrou A, Geronikaki A, Ivanov M, Kostic M, Sokovic M, Carazo A, Mlad ˇenka P, Sree- harsha N, Venugopala KN, Nair AB, Elsewedy HS. 5-Benzyli- den-2-(5-methylthiazol-2-ylimino)thiazolidin-4-ones as Anti- micro-bial Agents. Design, Synthesis, Biological Evaluation and Mo-lecular Docking Studies. Antibiot. 2021;10(3):309. doi:10.3390/antibiotics10030309 22. Abo-Bakr AM, Hassan EA, Mahdy A-HS, Zayed SE. Synthetic and biological studies on some new camphor thiazolidinones. J Iran Chem Soc. 2021;18(10):2757–2769. doi:10.1007/s13738-021-02228-6 23. Orchard MG, Neuss JC, Galley CM, Carr A, Porter DW, Smith P, Scopes DIC, Haydon D, Vousden K, Stubberfield CR, Young K, Page M. Rhodanine-3-acetic acid derivatives as inhibitors of fungal protein mannosyl transferase 1 (PMT1). Bioorg Med Chem Lett. 2004;14(15):3975–3978. doi:10.1016/j.bmcl.2004.05.050 24. Chaban T, Matiichuk Y, Chulovska Z, Tymoshuk O, Chaban I, Matiychuk V. Synthesis and biological evaluation of new 4- oxo-thiazolidin-2-ylidene derivatives as antimicrobial agents. Arch Pharm. 2021;354(7):2100037. doi:10.1002/ardp.202100037 25. Obydennov KL, Galushchinskiy AN, Kosterina MF, Glukha- reva TV, Morzherin YY. Synthesis of 4-(4-oxo-1,3-thiazolidin- 2-ylidene)-pyrrolidine-2,3,5-triones. Chem Heterocycl Compd. 2017;53(5):622–625. doi:10.1007/s10593-017-2102-0 26. Kolarević A, Ilić BS, Kocić G, Džambaski Z, Šmelcerović A, Bondžić BP. Synthesis and DNase I inhibitory properties of some 4‐thiazolidinone derivatives. J Cell Biochem. 2019;120(1):264–274. doi:10.1002/jcb.27339 27. Džambaski Z, Marković R, Kleinpeter E, Baranac-Stojanović M. 2-Alkylidene-4-oxothiazolidine S-oxides: synthesis and stereochemistry. Tetrahedron. 2013;69(31):6436–6447. doi:10.1016/j.tet.2013.05.087 28. Obydennov KL, Kalinina TA, Galieva NA, Beryozkina TV, Zhang Y, Fan Z, Glukhareva TV, Bakulev VA. Synthesis, fungi- cidal activity, and molecular docking of 2-acylamino and 2- thioacylamino derivatives of 1H-benzo[d]imidazoles as anti- tubulin agents. J Agric Food Chem. 2021;69(40):12048– 12062. doi:10.1021/acs.jafc.1c03325 29. Obydennov KL, Khamidullina LA, Galushchinskiy AN, Shatunova SA, Kosterina MF, Kalinina TA, Fan Zh, Glukhareva TV, Morzherin YuYu. Discovery of Methyl (5Z)-[2-(2,4,5-Tri- oxopyrrolidin-3-ylidene)-4-oxo-1,3-thiazolidin-5-ylidene]ace- tates as Antifungal Agents against Potato Diseases. J Agric Food Chem. 2018;66(24):6239–6245. doi:10.1021/acs.jafc.8b02151 30. Yu X, Teng P, Zhang Y-L, Xu Z-J, Zhang M-Z, Zhang W-H. De- sign, synthesis and antifungal activity evaluation of couma- rin-3-carboxamide derivatives. Fitoterapia. 2018;127:387– 395. doi:10.1016/j.fitote.2018.03.013 https://doi.org/10.15826/chimtech.2023.10.1.06 https://doi.org/10.15826/chimtech.2023.10.1.06 https://doi.org/10.1021/jm7012024 https://doi.org/10.1211/jpp.61.03.0008 https://doi.org/10.1016/j.ejmech.2006.03.029 https://doi.org/10.1021/jm050859x https://doi.org/10.1111/j.1747-0285.2010.01071.x https://doi.org/10.1016/j.bmc.2008.10.032 https://doi.org/10.1016/j.bmc.2008.02.001 https://doi.org/10.5562/cca2955 http://nopr.niscpr.res.in/handle/123456789/9197 https://doi.org/10.1021/jm201243p https://doi.org/10.1016/j.bbapap https://doi.org/10.1016/j.ejmech.2020.112870 https://doi.org/10.1002/ardp.201100082 https://doi.org/10.1016/j.compbiolchem.2017.02.008 https://doi.org/10.1016/j.bmcl.2012.08.052 https://doi.org/10.1016/j.carres.2006.09.010 https://doi.org/10.3390/antibiotics10030309 https://doi.org/10.1007/s13738-021-02228-6 https://doi.org/10.1016/j.bmcl.2004.05.050 https://doi.org/10.1002/ardp.202100037 https://doi.org/10.1007/s10593-017-2102-0 https://doi.org/10.1002/jcb.27339 https://doi.org/10.1016/j.tet.2013.05.087 https://doi.org/10.1021/acs.jafc.1c03325 https://doi.org/10.1021/acs.jafc.8b02151 https://doi.org/10.1016/j.fitote.2018.03.013