A Green Chemistry Approach to Thiazolidine-4-Carboxylic Acids: Design, Docking of Antiviral Activity

Abstract

Green chemistry principles advocate for the development of more sustainable synthetic methods by enhancing efficiency, minimizing toxic solvent usage, reducing reaction steps, and limiting chemical waste. In alignment with these principles, microwave-assisted synthesis was employed to rapidly construct a series of thiazolidine-4-carboxylic acid derivatives, inspired by the structure of the natural amino acid cysteine. To evaluate their therapeutic potential, drug-likeness, and safety profiles, computational analyses were conducted, including molecular docking by using Pyrx software. The combined experimental and computational results provide a promising foundation for the development of these compounds as potential pharmacological agents. Further research is currently being conducted to determine the antiviral efficacy of these thiazolidine-4-carboxylic acid derivatives.

Keywords

Introduction

Green chemistry was for mutated in the 1990s and includes 12 principles. The green processes diminish the adverse effects of any chemical reaction by following certain criteria viz. catalyst- and solvent-free synthesis and designing of biodegradable and less toxic products with high efficiency. In this review article, we have compiled researches which step ahead toward green chemistry. In the past few years, divergent synthetic strategies ^[1]have been introduced aimed at efficient and green synthesis using inexpensive reactants, nontoxic solvents, reusable catalysts, nanoparticle-catalyzed synthesis, and solvent-free synthesis with high yields using different techniques such as microwave irradiation (MWI), sonochemistry, surface chemistry and others. Multicom ponent reactions (MCRs) (Strecker, Ugi, Bucherer-Bergs, Biginelli) are excellent pathways for the synthesis of heterocycles ^[2]as they have all the features for ideal synthesis like simple procedure for generating complex hybrid molecules in fewer steps which possess excellent pharmaceutical activity with high atom economy and eco-friendliness ^[3,4]. The notable features of thiazolidine scaffolds compel us to study the literature and outline the status of thiazolidine, its derivatives and their biological significance.

Microwave-assisted organic synthesis of various heterocyclic moieties is an effective and environment-friendly synthetic approach and becoming an effective tool of green chemistry method ^[5]. Microwave irradiation is an effective form of heating depends on the capacity of analogues to translate electromagnetic energy into heat ^[6]. L-cysteine contains not only nitrogen, which is found in all amino acids, but also sulfur in its molecular structure, and these elements serve as heteroatom dopants with appropriate energy levels to enhance the blue emission intensity ^[7,8]; therefore, we chose L-cysteine as a carbon source in this study. One of the most eminent heterocyclic motifs, thiazolidine, is a five-membered heterocycle system having the formula C₃H₇NS containing one nitrogen and one sulfur atom, and which exhibits notable medicinal and pharmaceutical properties. In the thiazolidine nucleus, many substitutions are possible on 2, 4 and 5 positions responsible for enhancing the compound’s pharmaceutical importance. Thiazolidine and its composites are key components of many natural products and drugs and are also present in many synthetic compounds such as anticancer ^[9-12], antimicrobial ^[13-15], antitumor ^[16,17], antidiabetic ^[18], antiparasitic ^[19,20], anti-inflammatory ^[21-23], antitubercular ^[24], antifungal ^[25], antiviral ^[26,27], anti-HIV ^[28-30], cytotoxicity ^[31], antitrypanosomal ^[32], antinociceptive and anti-hypernociceptive com pounds ^[33].

Computational methods are now an important component of modern drug discovery ^[34] PyRx includes a docking wizard. Specific aspects for using PyRx as well as consideration for data preparation docking and data analysis also describes. Drug discovery is attractive research area that enables application of cutting edges biomedical research to improve health of man people by active components of natural origin have been under enormous investigation as potential studies that were performed by using PyRx docking tool through autodock vina software^[35].

MATERIAL AND METHODS:

Computational Methodology

The computational workflow in this study involved four major stages: molecular design, novelty verification, protein selection, and docking preparation.

1. Molecular Design using ChemSketch software (ACD/Labs) was utilized to construct and visualize the chemical structures of the target molecules. The software was also employed to determine key physicochemical properties, including molecular weight, molecular formula, logP (partition coefficient), molar refractivity, hydrogen bond donors and acceptors, polar surface area, and structural geometry. This initial computational analysis provided insights into the drug-likeness and potential chemical behavior of the designed compounds.

2. Novelty Check and Data Retrieval from PubChem, an open-access chemical database maintained by the National Center for Biotechnology Information (NCBI), was used to verify the novelty of the designed molecules by cross-referencing them with existing chemical entries. This ensured that the compounds were structurally unique. Additionally, PubChem provided information on the physicochemical nature, chemical classification, and reported biological activities of structurally similar molecules.

3. Protein Structure Selection from the Protein DataBank (PDB) was accessed to obtain three-dimensional crystal structures of relevant viral proteins. Specifically, PDB IDs 8EQS and 1XOE were selected based on their biological relevance, structural resolution, and availability of active site information. The structures were downloaded in .pdb format for subsequent docking studies.

8eqs

1xoe

4. Ligand and Protein Preparation using BIOVIA Discovery Studio: Visualizer was used to prepare the ligands and protein receptors for molecular docking. Designed ligands underwent energy minimization to achieve stable conformations. The protein structures were preprocessed by removing water molecules, adding hydrogen atoms, correcting bond orders, and optimizing geometry. This preparation ensured that both ligand and receptor structures were in optimal form for accurate docking simulations.

5. PyRx Molecular Docking Steps

1. Install and Launch PyRx

• Download PyRx (latest stable version) from the official website.
• Install and open the software.
• The interface will have Molecule View, Vina Wizard, and other panels.

2. Prepare Ligands

1. Obtain ligand structures:
   1. Download .sdf files from PubChem or draw them in ChemSketch and save as .sdf.
2. Convert to PDBQT:
   1. In PyRx, click Open Ligand → select .sdf.
   2. Right-click → Convert to AutoDock Ligand (pdbqt).
3. Energy minimization:
   1. In Molecule View, select the ligand.
   2. Go to Tools → Minimize Energy.
   3. Choose Force Field and run minimization.

3. Prepare Protein (Target)

1. Obtain protein structure:
   1. Download .pdb file from RCSB PDB.
2. Clean the protein:
   1. Remove water molecules and unwanted ligands using software like Discovery Studio.
3. Convert to pdbqt:
   1. In PyRx, click Open Molecule → select .pdb.
   2. Right-click → Convert to AutoDock Macromolecule (pdbqt).

4. Set Docking Parameters

1. Switch to Vina Wizard.
2. Select Ligand and Macromolecule from dropdown menus.
3. Set Grid Box:
   1. Click Grid Box → Adjust Center (X, Y, Z) and Dimensions to cover the binding site.
4. Keep other settings default unless optimization is needed.

5. Run Docking

• Click Run Vina.
• PyRx will dock each ligand to the target and display docking scores (binding affinities in kcal/mol).

6. View and Save Results

1. Check scores:
   1. Lower (more negative) binding affinity values indicate better predicted binding.
2. Export docked poses:
   1. Right-click results → Save as PDBQT or Save as SDF for visualization in PyMOL or Discovery Studio.

7. Post-Docking Analysis

• Visualize interactions (hydrogen bonds, hydrophobic contacts) in PyMOL, Chimera, or Discovery Studio.
• Compare docking scores with standard/reference drugs.

RESULTS AND DISCUSSION

Table 1: Designed derivative of thiazolidine 4 carboxylic acid

COMPOUND	STURCTURE	IUPAC
DERI 1		(4R)-2-(4-sulfophenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 2		(4R)-2-(1H-imidazol-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 3		(4R)-2-[1-(pyrimidin-2-yl)-1H-imidazol-2-yl]-1,3-thiazolidine-4-carboxylic acid
DERI 4		(4R)-2-(1-benzyl-1H-imidazol-4-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 5		(4R)-2-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 6		(4R)-2-[4-hydroxy-5-(hydroxymethyl) oxolan-2-yl]-1,3-thiazolidine-4-carboxylic acid
DERI 7		(4R)-2-(1H-1,2,4-triazol-1-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 8		(4R)-2-[(1E)-6-methylhepta-1,5-dien-1-yl]-1,3-thiazolidine-4-carboxylic acid
DERI 9		(4R)-2-(pyrrolidin-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 10		(4R)-2-(6-chloropyridin-3-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 11		(4R)-2-octyl-1,3-thiazolidine-4-carboxylic acid
DERI 12		(4R)-2-(piperidin-4-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 13		(4R)-2-(3H-indol-5-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 14		(4R)-2-(1H-1,3-benzimidazol-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 15		(4R)-2-(4,5-dihydro-1,3-oxazol-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 16		(4R)-2-{[2-(methylsulfanyl) phenyl] methyl}-1,3-thiazolidine-4-carboxylic acid
DERI 17		(4R)-2-(2-hydroxy-5-iodophenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 18		(4R)-2-(2-cyclopentylethyl)-1,3-thiazolidine-4-carboxylic acid
DERI 19		(4R)-2-[4-(diethylamino) phenyl]-1,3-thiazolidine-4-carboxylic acid
DERI 20		(4R)-2-(3-chloro-2-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 21		(4R)-2-(4-tert-butyl-2-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 22		(4R)-2-(2-hydroxy-3-nitrophenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 23		(4R)-2-(5-phenylfuran-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 24		(4R)-2-(3-chloro-5-fluoro-2-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 25		(4R)-2-(3-tert-butyl-2,5-dihydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 26		(4R)-2-[4-(pyridin-2-yl) phenyl]-1,3-thiazolidine-4-carboxylic acid
DERI 27		(4R)-2-(1-methyl-1H-imidazol-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 28		(4R)-2-(5-methyl-1,2-oxazol-3-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 29		(4R)-2-(2,3,5,6-tetramethylphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 30		(4R)-2-[1-(benzenesulfonyl)-1H-pyrrol-2-yl]-1,3-thiazolidine-4-carboxylic acid
DERI 31		(4R)-2-[2-(methylsulfanyl) phenyl]-1,3-thiazolidine-4-carboxylic acid
DERI 32		(4R)-2-(2-bromo-3-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 33		(4R)-2-(3-bromo-5-chlorophenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 34		(4R)-2-(4-bromofuran-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 35		(4R)-2-(4-chlorofuran-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 36		(4R)-2-{4-[bis(2-chloroethyl) amino] phenyl}-1,3-thiazolidine-4-carboxylic acid
DERI 37		(4R)-2-{4-[bis(hydroxymethyl)amino] phenyl}-1,3-thiazolidine-4-carboxylic acid
DERI 38		(4R)-2-(5-sulfofuran-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 39		(4R)-2-(4-tert-butoxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 40		(4R)-2-(1,2-dihydroacenaphthylen-5-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 41		(4R)-2-([2,2'-bithiophen]-5-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 42		(4R)-2-(2,4-dihydroxypyrimidin-5-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 43		(4R)-2-(3,5-dipropylphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 44		(4R)-2-(5-chloro-2-hydroxyphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 45		(4R)-2-(2-formylphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 46		(4R)-2-(3-formylphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 47		(4R)-2-(4-formylphenyl)-1,3-thiazolidine-4-carboxylic acid
DERI 48		(4R)-2-[3-carboxy-4-(pyridin-2-yl) phenyl]-1,3-thiazolidine-4-carboxylic acid
DERI 49		(4R)-2-(3-methyl-5-sulfofuran-2-yl)-1,3-thiazolidine-4-carboxylic acid
DERI 50		(4R)-2-(2-hydroxy-3,5-dipropylphenyl)-1,3-thiazolidine-4-carboxylic acid

Table 2: PYRX DOCKING SCORE BINDING AFFINITY

SR.NO	COMPOUND	8EQS	1XOE
	ACYCLOVIR	-6.8	-7.1
	OSELTAMIVIR	-6.2	-6.2
	AMANTADINE	-5.5	-5.8
	INDINAVIR	-10.8	-9.2
	RIBAVIRIN	-7.2	-6.7
	DERI 1	-7.5	-6.1
	DERI 2	-6.4	-5.7
	DERI 3	-7.6	-7.5
	DERI 4	-7.6	-6.8
	DERI 5	-8.5	-8
	DERI 6	-6.6	-5.8
	DERI 7	-6.6	-5.7
	DERI 8	-6.2	-5.2
	DERI 9	-6.5	-5.8
	DERI 10	-6.7	-5.9
	DERI 11	-5.1	-4.7
	DERI 12	-6.5	-5.6
	DERI 13	-7.1	-6.8
	DERI 14	-7.3	-6.8
	DERI 15	-6.4	-5.7
	DERI 16	-6.6	-5.6
	DERI 17	-7	-6.3
	DERI 18	-6.4	-5.7
	DERI 19	-6.6	-5.7
	DERI 20	-6.6	-6
	DERI 21	-7.1	-6.6
	DERI 22	-7.5	-6.4
	DERI 23	-7.2	-7.3
	DERI 24	-6.9	-6.6
	DERI 25	-7.3	-6.4
	DERI 26	-7.9	-6.9
	DERI 27	-6.4	-5.9
	DERI 28	-6.8	-6.3
	DERI 29	-7	-6.2
	DERI 30	-7.1	-7.7
	DERI 31	-6.6	-6.1
	DERI 32	-7.5	-6.6
	DERI 33	-6.7	-6.3
	DERI 34	-6.4	-5.6
	DERI 35	-6.5	-5.7
	DERI 36	-6.6	-5.7
	DERI 37	-7	-6.2
	DERI 38	-7	-6.3
	DERI 39	-7.1	-6.1
	DERI 40	-8	-7.5
	DERI 41	-6.9	-6
	DERI 42	-7.4	-7.1
	DERI 43	-6.8	-7.3
	DERI 44	-6.6	-6.5
	DERI 45	-7.4	-6.3
	DERI 46	-7.1	-6
	DERI 47	-7.4	-5.7
	DERI 48	-8.2	-6.8
	DERI 49	-7.4	-6.6
	DERI 50	-6.9	-6.6

Table 3: Ligand interaction and 2d structure of the docked molecules

COMPOUND	Ligand interaction	2d
Deri 1
DERI 2
DERI 3
DERI 4
DERI 5
DERI 6
DERI 7
DERI 8
DERI 9
DERI 10
DERI 11
DERI 12
DERI 13
DERI 14
DERI 15
DERI 16
DERI 17
DERI 18
DERI 19
DERI 20
DERI 21
DERI 22
DERI 23
DERI 24
DERI 25
DERI 26
DERI 27
DERI 28
DERI 29
DERI 30
DERI 31
DERI 32
DERI 33
DERI 34
DERI 35
DERI 36
DERI 37
DERI 38
DERI 39
DERI 40
DERI 41
DERI 42
DERI 43
DERI 44
DERI 45
DERI 46
DERI 47
DERI 48
DERI 49
DERI 50

The molecular docking analysis using PyRx was performed for standard antiviral drugs and fifty designed derivatives (DERI 1–50) against two target proteins, 8EQS and 1XOE. The binding affinities (kcal/mol) are presented in Table 2.

Among the standard drugs, Indinavir exhibited the highest binding affinity towards both targets, recording −10.8 kcal/mol (8EQS) and −9.2 kcal/mol (1XOE). This was followed by Ribavirin (−7.2, −6.7) and Acyclovir (−6.8, −7.1). Oseltamivir and Amantadine showed comparatively lower affinities, with docking scores in the range of −5.5 to −6.2 kcal/mol.

Several derivatives demonstrated binding affinities comparable to or exceeding those of the standard drugs. Against 8EQS, the top-performing derivatives included DERI 5 (−8.5), DERI 40 (−8.0), DERI 48 (−8.2), and DERI 26 (−7.9), indicating strong potential for target inhibition. For 1XOE, DERI 30 (−7.7), DERI 42 (−7.1), DERI 43 (−7.3), and DERI 40 (−7.5) displayed notable affinities, rivaling or surpassing Acyclovir.

The differences in binding scores between the two proteins suggest that certain derivatives may exhibit target selectivity. For example, DERI 48 showed strong affinity for 8EQS but moderate interaction with 1XOE, while DERI 30 was more effective against 1XOE. This variation could be attributed to differences in the active site architecture, hydrophobicity, and hydrogen-bonding patterns of the two proteins.

CONCLUSION:

Overall, these docking results indicate that multiple derivatives, particularly DERI 5, DERI 40, DERI 48, and DERI 30, possess significant inhibitory potential. Their performance against both targets highlight their promise as lead compounds for further optimization. However, as docking results are predictive in nature, molecular dynamics simulations, ADMET profiling, and in vitro assays are necessary to validate these computational findings and assess their drug-likeness and biological activity.

ACKNOWLEDGEMENT:

The author wishes to thank Sakthi Arul Thiru Amma and Thirumathi Amma ACMEC Trust, providing facilities to do the work in successful manner. We are grateful to thank our Dean Research and academic Prof. Dr. T. Vetrichelvan, M. Pharm., Ph. D. and our Principal Dr. D. Nagavalli M. Pharm., Ph.D for the kind support and encouraging for the completion of the work. Finally, thanks to my family and friends.

REFERENCES

1. Maleki A, Ghassemi M, Firouzi-Haji R (2014) Green multicomponent synthesis of four different classes of six-membered N-containing and O-containing heterocycles catalyzed by an efficient chi tosan-based magnetic bionanocomposite. Pure Appl Chem. https://doi.org/10.1515/pac-2017-0702
2.  Maleki A (2013) One-pot multicomponent synthesis of diazepine derivatives using terminal alkynes in the presence of silica-supported superparamagnetic iron oxide nanoparticles. Tetrahe dron Lett 54:2055–2059
3.  Maleki A (2014) One-pot three-component synthesis of pyrido [2′,1′:2,3]imidazo[4,5-c]iso quinolines using Fe3O4@SiO2–OSO3H as an efficient heterogeneous nanocatalyst. RSC Adv 4:64169–64173
4. A. Upadhyay, S.K. Srivastava, S.D. Srivastava, Conventional and microwave assisted synthesis of Some new N-[(4-oxo-2-substituted aryl 1, 3-thiazolidine)-acet amidyl]-5-nitroindazoles and its antimicrobial activity, Eur. J. Med. Chem. 45 (9) (2010) 3541–3548.
5. W. Cunico, W.T. Vellasco Junior, M. Moreth, C.R. Gomes, Microwave-assisted synthesis of 1, 3-thiazolidin-4-ones and 2-aryl-1, 3-oxathiolan-5-ones, Lett. Org. Chem. 5 (5) (2008) 349–352.
6. Y. Dong, H. Pang, H.B. Yang, C. Guo, J. Shao, Y. Chi, C.M. Li, T. Yu, Carbon-based dots co-doped with nitrogen and sulfur for high quantum yield and excitation-in dependent emission, Angew. Chem. Int. Ed. 52 (2013) 7800–7804 https://doi.org/ 10.1002/anie.201301114.
7. H. Li, F.-Q. Shao, H. Huang, J.-J. Feng, A.-J. Wang, Eco-friendly and rapid micro wave synthesis of green fluorescent graphitic carbon nitride quantum dots for vitro bioimaging, Sens. Actuators, B 226 (2016) 506–511 https://doi.org/10.1016/j.snb. 2015.12.018.
8. Zhang Q, Zhou H, Zhai S, Yan B (2010) Natural product-inspired synthesis of thiazolidine and thiazolidinone compounds and their anticancer activities. Curr Pharm Des 16:1826–1842
9. Havrylyuk D, Zimenkovsky B, Vasylenko O, Lesyka R (2013) Synthesis and anticancer and antivi ral activities of new 2-pyrazoline-substituted 4-thiazolidinones. J Heterocycl Chem 50:E55–E62
10.  Osmaniye D, Levent S, Ard?ç CM, Atl? Ö, Özkay Y, Kaplanc?kl? ZA (2017) Synthesis and antican cer activity of some novel benzothiazole-thiazolidine derivatives. Phosphorus Sulfur Silicon Relat Elem 193:249–256
11.  El-Gaby MSA, Ismail ZH, Abdel-Gawad SM, Aly HM, Ghorab MM (2009) Synthesis of thiazoli dine and thiophene derivatives for evaluation as anticancer agents. Phosphorus Sulfur Silicon Relat Elem 184:2645–2654
12. Agarwal S, Agarwal DK, Gautam N, Agarwal K, Gautam DC (2014) Synthesis and in vitro anti microbial evaluation of benzothiazole incorporated thiazolidin-4-ones derivatives. J Korean Chem Soc 58:33–38 
13.  Sankar PS, Divya K, Padmaja A, Padmavathi V (2017) Synthesis and antimicrobial activity of aze tidinone and thiazolidinone derivatives from azolylindolyl Schiff’s bases. Med Chem 7:340–347
14. Deep A, Kumar P, Narasimhan B, Ramasamy K, Mani V, Mishra RK, Majeed ABA (2015) Synthe sis, antimicrobial, anticancer evaluation of 2-(aryl)-4- thiazolidinone derivatives and their QSAR studies. Curr Top Med Chem 15:990–1002
15.  Gouda MA, Abu-Hashem AA (2011) Synthesis, characterization, antioxidant and antitumor evaluation of some new thiazolidine and thiazolidinone derivatives. Arch Pharm Chem Life Sci 11:170–177
16.  Nishida S, Maruoka H, Yoshimura Y, Goto T, Tomita R, Masumoto E, Okabe F, Yamagata K, Fujioka T (2012) Synthesis and biological activities of some new thiazolidine derivatives contain ing pyrazole ring system. J Heterocycl Chem 49:303–309
17.  Datar PA, Aher SB (2016) Design and synthesis of novel thiazolidine-2,4-diones as hypoglycemic agents. J Saudi Chem Soc 20:S196–S201
18. Moreira DRM, Costa SPM, Hernandes MZ, Rabello MM, de Oliveria Filho GB, de Melo Cris tiane ML, da Rocha LF, de Simone CA, Ferreira RS, Fradico JRB, Meira CS, Guimarães ET, Srivastava RM, Pereira VRA, Soares MBP, Leite ACL (2012) Structural investigation of anti Trypanosoma cruzi 2-iminothiazolidin-4-ones allows the identification of agents with efficacy in infected mice. J Med Chem 55:10918–10936
19.  Zehetmeyr FK, Pereira da Silva MAM, Pereira KM, Berne MEA, Cunico W, Júnior JCC, Gou vea DP, da Silva Nascente P, de Oliveria Hübner S, Siqueira GM (2018) Ovicidal in vitro activ ity of 2-aryl-3-(2-morpholinoethyl)thiazolidin-4-ones and 2-aryl-3-(3-morpholinopropyl)thia zolidin-4-ones against Fasciola hepatica (Linnaeus, 1758). Exp Parasitol 192:60–64
20.  Geronikaki AA, Lagunin AA, Hadjipavlou-Litina DI, Eleftheriou PT, Filimonov DA, Poroikov VV, Alam I, Saxena AK (2008) Computer-aided discovery of anti-inflammatory thiazolidinones with dual cyclooxygenase/lipoxygenase inhibition. J Med Chem 51:1601–1609 1 3 Topics in Current Chemistry (2020) 378:34 Page 83 of 90 34
21.  Ma L, Xie C, Ma Y, Liu J, Xiang M, Ye X, Zheng H, Chen Z, Xu Q, Chen T, Chen J, Yang J, Qiu N, Wang G, Liang X, Peng A, Yang S, Wei Y, Chen L (2011) Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives for the treatment of inflam matory diseases. J Med Chem 54:2060–2068
22. Barros CD, Amato AA, de Oliveira TB, Iannini KBR, da Silva AL, da Silva TG, Leite ES, Hernandes MZ, de Lima MCA, Galdino SL, de Asis Rocha Neves F, da Rocha Pitta I (2010) Synthesis and anti-inflammatory activity of new arylidene-thiazolidine-2,4-diones as PPARγ ligands. Bioorg Med Chem 18:3805–3811
23.  Chilamakuru NB, Shankaranath V, Rajasekhar KK, Singirisetty T (2013) Synthesis, characteri sation and anti-tubercular activity of some new 3,5-disubstituted-2,4-thiazolidinediones. Asian J Pharm Clin Res 6:29–33
24.  Siddiqui IR, Singh PK, Singh J, Singh J (2003) Synthesis and fungicidal activity of novel 4,4′-bis(2″-aryl-5″-methyl/unsubstituted-4″-oxo-thiazolidin-3″-yl) bibenzyl. J Agric Food Chem 51:7062–7065 25. Nitsche C, Schreier VN, Behnam MAM, Kumar A, Bartenschlager R, Klein CD (2013) Thi azolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture. J Med Chem 56:8389–8403
25.  Romine JL, St. Laurent DR, Leet JE, Martin SW, Serrano-Wu MH, Yang F, Gao M, O’Boyle DR, Lemm JA, Sun JH, Nower PT, Huang X, Deshpande MS, Meanwell NA, Snyder LB (2011) Inhibitors of HCV NS5A: from iminothiazolidinones to symmetrical stilbenes. ACS Med Chem Lett 2:224–229
26.  Jiang S, Tala SR, Lu H, Abo-Dya NE, Avan I, Gyanda K, Lu L, Katritzky AR, Debnath AK (2011) Design, synthesis, and biological activity of novel 5-((arylfuran/1H-pyrrol-2-yl) methylene)-2-thioxo-3-(3-(trifluoromethyl)phenyl)thiazolidin-4-ones as HIV-1 fusion inhibitors targeting gp41. J Med Chem 54:572–579
27.  Barreca ML, Balzarini J, Chimirri A, De Clercq E, De Luca L, Holtje HD, Holtje M, Monforte AM, Monforte P, Pannecouque C, Rao A, Zappala M (2002) Design, synthesis, structure-activ ity relationships, and molecular modeling studies of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV agents. J Med Chem 45:5410–5413
28. Rawal RK, Tripathi R, Katti SB, Pannecouquec C, De Clercq E (2007) Design, synthesis, and evaluation of 2-aryl-3-heteroaryl-1,3- thiazolidin-4-ones as anti-HIV agents. Bioorg Med Chem 15:1725–1731 30. Janovec L, Sabolová D, Kožurková M, Paulíková H, Kristian P, Ungvarský J, Morav?íková E, Bajdichova M, Podhradsky D, Imrich J (2007) Synthesis, DNA interaction, and cytotoxic activ ity of a novel proflavine-dithiazolidinone pharmacophore. Bioconjugate Chem 18:93–100
29.  Patrick DA, Gillespie JR, McQueen J, Hulverson MA, Ranade RM, Creason SA, Herbst ZM, Gelb MH, Buckner FS, Tidwell RR (2017) Urea derivatives of 2-aryl-benzothiazol-5-amines: a new class of potential drugs for human African trypanosomiasis. J Med Chem 60:957–971
30. Pavin NF, Donato F, Cibin FW, Jesse CR, Schneider PH, de Salles HD, Amaral Soares L, Alves D, Savegnago L (2011) Antinociceptive and anti-hypernociceptive effects of Se-phenyl thiazoli dine-4-carboselenoate in mice. Eur J Pharmacol 668:169–176
31. Klebe G (2006) Virtual ligand screening: strategies, perspectives, and limitations. Drug Discov Today 11:580–594
32. M. venkateshan, J. Suresh, M. Muthu, R. Ranjith Kumar, chemical data collection 28(2020).
33. Yu W. and MacKerell A. D. - Computer-Aided Drug Design Methods, In: Antibiotics, Chapter Chapter 5, 2017, pp. 85-106.
34.  Marshall G. R. - Computer-Aided Drug Design, Annu. Rev. Pharmacol Toxicol 27 (1) (1987) 193-213. https://doi.org/10.1146/annurev.pa.27.040187.001205.
35. Pham M. Q., Tran T. H. V., Pham Q. L., and Gairin J. E. - In silico analysis of the binding properties of solasonine to mortalin and p53, and in vitro pharmacological studies of its apoptotic and cytotoxic effects on human HepG2 and Hep3b hepatocellular carcinoma cells, Fundam. Clin. Pharmacol 33 (4) (2019) 385-396. https://doi.org/10.1111/fcp.12447.