Synthesis of Thiazolidinone-Thiadiazole Hybrids: Molecular Docking and Antimicrobial Evaluation
DOI:
https://doi.org/10.14500/aro.12797Keywords:
Antimicrobial activity, Green organic chemistry, Molecular docking studies, Multidrug resistant, ThiazolidinonesAbstract
A green synthesis of bis-thiazolidinone-thiadiazole hybrids (6a-h) exhibiting mild to potent antibacterial activity is reported. The hybrid compounds were synthesized in one-pot three-component Microwave-assisted reaction under solvent free condition from the corresponding bis- thiadiazole amines (3) reaction with various aldehydes, and thioglycolic acid. The products were obtained in acceptable yields and characterized based on spectroscopic techniques (Fourier transform infrared, proton nuclear magnetic resonance, carbon-13 nuclear magnetic resonance, and carbon-attached proton test nuclear magnetic resonance). Antibacterial screening was performed on the synthesized compounds (6a-h) against both Grampositive strains (Staphylococcus and Streptococcus) and Gramnegative strains (Escherichia coli and Klebsiella pneumoniae), with their efficacy compared to the reference antibiotics ciprofloxacin and vancomycin. Overall, the synthesized compounds demonstrated highly antibacterial properties. Among the series, compounds (6b, 6d, and 6e) exhibited broad-spectrum and potent levels of antibacterial activity against species; furthermore, they showed notable activity against K. pneumoniae as the most antibacterial-resistant pathogen. The result of Molecular docking studies indicated that OH, OCH3 substituents, such as in compounds (6b), enhanced binding ability interaction and producing conventional hydrogen bond with the minimum energy affinity ( ∆G).
Downloads
References
Abeed, A.A.O., and Abdel-Mohsen, S.A., 2013. Synthesis, characterization and antimicrobial activity of new thiadiazoles, thiazolidines, and spiro (indole azoles) linked to 2-pyrazolin-5-one. European Journal of Scientific Research, 108(2), pp.279-294.
Abo‐Bakr, A.M., and Hashem, H.E., 2019. New 1, 3, 4‐thiadiazole derivatives: Synthesis, characterization, and antimicrobial activity. Journal of Heterocyclic Chemistry, 56(3), pp.1038-1047.
Abo-Bakr, A.M., Hassan, E.A., Mahdy, A.S., and Zayed, S.E., 2021. Synthetic and biological studies on some new camphor thiazolidinones. Journal of the Iranian Chemical Society, 18(10), pp.2757-2769.
Aggarwal, N., Jain, S., and Chopra, N., 2022. Hybrids of thiazolidin-4-ones and 1, 3, 4-thiadiazole: Synthesis and biological screening of a potential new class of acetylcholinesterae inhibitors. Biointerface Research in Applied Chemistry, 12, pp.2800-2812.
AL-Abayechi, M.M.H., Al-Nayili, A., and Balakit, A.A., 2024. Green synthesis of 1, 3-Thiazolidin-4-ones derivatives by using acid-activated montmorillonite as catalyst. Inorganic Chemistry Communications, 161, p.112076.
Al-Khyaat, A., 2020. Preparation and identification of some new thiazolidine-4 one compounds from Schiff base derivatives. Journal of Education and Science, 29(3), pp.142-156.
Bakht, J., Ali, H., Khan, MA., Khan, A., Saeed, M., Shafi, M., Islam, A., and Tayyab, M., 2011. Antimicrobial activities of different solvents extracted samples of Linum usitatissimum by disc diffusion method. African Journal of Biotechnology, 10(85), pp.19825-19835.
Barreca, M.L., Chimirri, A., De Luca, L., Monforte, A.M., Monforte, P., Rao, A., Zappalà, M., Balzarini, J., De Clercq, E., Pannecouque, C., and Witvrouw, M., 2001. Discovery of 2, 3-diaryl-1, 3-thiazolidin-4-ones as potent anti-HIV-1 agents. Bioorganic and Medicinal Chemistry Letters, 11(13), pp.1793-1796.
Baviskar, B.A., Khadabadi, S.S., and Deore, S.L., 2013, Synthesis and evaluation of some new thiazolidin‐4‐one derivatives as potential antimicrobial agents. Journal of Chemistry, 2013(1), p.656271.
CambridgeSoft Corporation, 1986. ChemDraw. CambridgeSoft Corporation, Cambridge, MA, USA. Chaban, T., Matiichuk, Y., Chulovska, Z., Tymoshuk, O., Chaban, I., and Matiychuk, V., 2021. Synthesis and biological evaluation of new 4‐oxo thiazolidin‐2‐ylidene derivatives as antimicrobial agents. Archiv Der Pharmazie, 354(7), p.2100037.
Cunico, W., Gomes, C.R.B., Ferreira, M.L.G., Capri, L.R., Santos, M.R.L., Sa, P.M., Boechat, S., Bastos, M.M., Maciel, L.C., and Mayer, L.M.U., 2007. One-pot synthesis of 1, 3-thiazolidin-4-ones derivatives from 2-amino-1, 3, 4-thiadiazole. Letters in Organic Chemistry, 4(7), pp.505-508.
Desai, K.G., and Desai, K.R., 2006. A facile microwave enhanced synthesis of sulfur-containing 5-membered heterocycles derived from 2-mercaptobenzothiazole over ZnCl 2/DMF and antimicrobial activity evaluation. Journal of Sulfur Chemistry, 27(4), pp.315-328.
Diurno, M.V., Mazzoni, O., Piscopo, E., Calignano, A., Giordano, F., and Bolognese, A., 1992. Synthesis and antihistaminic activity of some thiazolidin 4-ones. Journal of Medicinal Chemistry, 35(15), pp.2910-2912.
Drzał, W., and Trotsko, N., 2025. Review of recent advances in thiazolidin-4 one derivatives as promising antitubercular agents (2021–Present). Molecules, 30(10), p.2201.
Dwivedi, B., Bhardwaj, D., and Choudhary, D., 2024. Green design and synthesis of some novel thiazolidinone appended benzothiazole–triazole hybrids as antimicrobial agents. RSC Advances, 14(12), pp.8341-8352.
El Azab, I.H., and Abdel-Hafez, S.H., 2015. One-pot three-component microwave-assisted synthesis of novel thiazolidinone derivatives containing thieno [d] pyrimidine-4-one moiety as potential antimicrobial agents. Russian Journal of Bioorganic Chemistry, 41(3), pp.315-323.
Fesatidou, M., Petrou, A., and Geronikaki, A., 2024. Design, synthesis, biological evaluation and molecular docking studies of new thiazolidinone derivatives as NNRTIs and SARS‐CoV‐2 main protease inhibitors. Chemistry and Biodiversity, 21(12), p.e202401697.
Fesatidou, M., Zagaliotis, P., Camoutsis, C., Petrou, A., Eleftheriou, P., Tratrat, C., Haroun, M., Geronikaki, A., Ciric, A., and Sokovic, M., 2018. 5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design, synthesis, molecular docking and evaluation. Bioorganic and Medicinal Chemistry, 26(16), pp.4664-4676.
Gummidi, L., Kerru, N., Ebenezer, O., Awolade, P., Sanni, O., Islam, M.S., and Singh, P., 2021. Multicomponent reaction for the synthesis of new 1, 3, 4-thiadiazole thiazolidine-4-one molecular hybrids as promising antidiabetic agents through α-glucosidase and α-amylase inhibition. Bioorganic Chemistry, 115, p.105210.
Hamad, H.Q., Taher, S.G., and Aziz, D.M., 2022. Synthesis and molecular docking studies of new series of bis-Schiff bases Thiadiazoles derived from disulfides and thioethers with potent antibacterial properties. Science Journal of University of Zakho, 10(3), pp.130-139.
Hassan, S.A., and Aziz, D.M., 2021. Synthesis of new series bis-3-chloro-β lactam derivatives from symmetrical bis-Schiff bases as effective antimicrobial agents with molecular docking studies. Science Journal of University of Zakho, 9(3), pp.128-137.
Hussein, S.S., Ali, K.F., and Al-Saady, F.A., 2023. Synthesis, characterization, molecular docking, and preliminary antimicrobial evaluation of thiazolidinone derivatives. Palestinian Medical and Pharmaceutical Journal, 9(2), pp.181-192.
Jackson, C.M., Blass, B., Coburn, K., Djandjighian, L., Fadayel, G., Fluxe, A.J., Hodson, S.J., Janusz, J.M., Murawsky, M., Ridgeway, J.M., White, R.E., and Wu, S., 2007. Evolution of thiazolidine-based blockers of human Kv1. 5 for the treatment of atrial arrhythmias. Bioorganic and Medicinal Chemistry Letters, 17(1), pp.282-284.
Kasmi-Mir, S., Djafri, A., Paquin, L., Hamelin, J., and Rahmouni, M., 2006. One-pot synthesis of 5-arylidene-2-imino-4-thiazolidinones under microwave irradiation. Molecules, 11(8), pp.597-602.
Kumar, G., Seboletswe, P., Gcabashe, N., Dhawan, S., Manhas, N., Bhargava, G., Kumar, R., and Singh, P., 2025. Rapid and environmentally‐friendly synthesis of thiazolidinone analogues in deep eutectic solvent complemented with computational studies. Chemistry Open, 14(2), p.e202400198.
Kumar, Y., Matta, A., Kumar, P., Parmar, V.S., Van der Eycken, E.V., and Singh, B.K., 2015. Cu (I)-catalyzed microwave-assisted synthesis of 1, 2, 3-triazole linked with 4-thiazolidinones: A one-pot sequential approach. RSC Advances, 5(2), pp.1628-1639.
Murray, C.J.L., Ikuta, K.S., Sharara, F., Swetschinski, L., Aguilar, G.R., Gray, A., et al., 2022. Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 399(10325), pp.629-655.
Nasab, N.H., Raza, H., Eom, Y.S., Hassan, M., Kloczkowski, A., Chetty, L.C., Kruger, H.G., and Kim, S.,J., 2023. Design, synthesis, and in vitro and in silico studies of 1, 3, 4-thiadiazole-thiazolidinone hybrids as carbonic anhydrase inhibitors. New Journal of Chemistry, 47(29), pp.13710-13720.
Patel, H.M., Noolvib, M.N., Sethic, N.S., Gadadd, A.K., and Cameotra, S.S., 2017. Synthesis and antitubercular evaluation of imidazo [2, 1-b][1, 3, 4] thiadiazole derivatives. Arabian Journal of Chemistry, 10, pp.S996-S1002.
Patel, H.M., Rajani, D.P., Sharma, M.G., and Bhatt, H.G., 2019. Synthesis, molecular docking and biological evaluation of mannich products based on thiophene nucleus using ionic liquid. Letters in Drug Design and Discovery, 16(2), pp.119-126.
Petrow, V., Stephenson, O., Thomas, A.J. and Wild, A.M. 1958. Preparation and hydrolysis of some derivatives of 1: 3: 4-thiadiazole. Journal of the Chemical Society, pp.1508-1513.
Samir, A.H., Ali, K.F., and Saeed, R.S., 2017. Synthesis and characterization of some new thiazine, azetidine and thiazolidine compounds containing 1, 3, 4thiadiazole moiety and their antibacterial study. Ibn AL-Haitham Journal For Pure and Applied Science, 27(3), pp.350-364.
Sharma, A., Sharma, D., Saini, N., Sharma, S.V., Thakur, V.K., Goyal, R.K., and Sharma, R.C., 2023. Recent advances in synthetic strategies and SAR of thiazolidin-4-one containing molecules in cancer therapeutics. Cancer and Metastasis Reviews, 42(3), pp.847-889.
Singh, S., Dey, H., Kaira, M., Pandey, K.C., and Tahlan, S., 2026. Recent developments in heterocyclic derivatives as novel cancer therapeutics: From 2020-2024. Mini Reviews in Medicinal Chemistry.
Solomon, V.R., Haq, W., Srivastava, K., Puri, S.K., and Katti, S.B., 2007. Synthesis and antimalarial activity of side chain modified 4-aminoquinoline derivatives. Journal of Medicinal Chemistry, 50(2), pp.394-398.
Tahghighi, A., and Babalouei, F., 2017. Thiadiazoles: The appropriate pharmacological scaffolds with leishmanicidal and antimalarial activities: A review. Iranian Journal of Basic Medical Sciences, 20(6), p.613.
Tratrat, C., Petrou, A., Fesatidou, M., Haroun, M., Chohan, M., and Geronikaki, A., 2025. Rational design, synthesis, and biological evaluation of novel thiazole/thiazolidinones multitarget anti-human immunodeficiency virus molecules. Pharmaceuticals, 18(3), p.298.
World Health Organization., 2024. WHO Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance, to Guide Research, Development, and Strategies to Prevent and Control Antimicrobial Resistance. World Health Organization, Geneva.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Salam Gh. Taher
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Authors who choose to publish their work with Aro agree to the following terms:
-
Authors retain the copyright to their work and grant the journal the right of first publication. The work is simultaneously licensed under a Creative Commons Attribution License [CC BY-NC-SA 4.0]. This license allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
-
Authors have the freedom to enter into separate agreements for the non-exclusive distribution of the journal's published version of the work. This includes options such as posting it to an institutional repository or publishing it in a book, as long as proper acknowledgement is given to its initial publication in this journal.
-
Authors are encouraged to share and post their work online, including in institutional repositories or on their personal websites, both prior to and during the submission process. This practice can lead to productive exchanges and increase the visibility and citation of the published work.
By agreeing to these terms, authors acknowledge the importance of open access and the benefits it brings to the scholarly community.
Accepted 2026-04-01
Published 2026-06-19
ARO Journal is a scientific, peer-reviewed, periodical, and diamond OAJ that has no APC or ASC.