Synthesis, Characterization and Antibacterial Evaluation of Novel Thiazolidine Derivatives

Shaima H. Abdullah ^1*, Mahmoud M. Salih ¹, Khalid, A. Al-Badrany ^1*

Thiazolidine derivatives, synthesized from heterocyclic compounds, exhibit diverse biological activities, including antibacterial effects against various bacterial strains, suggesting potential pharmaceutical applications.

Abstract

Background: Heterocyclic compounds, which incorporate atoms such as nitrogen and sulfur alongside carbon, play a crucial role in nature and organic chemistry. Thiazolidine derivatives, characterized by sulfur and nitrogen atoms with a carbonyl group at the -4 position, are particularly noteworthy for their stability and diverse biological activities. We synthesized novel thiazolidine derivatives and determined their antibacterial properties. the synthesis of novel thiazolidine compounds was perforemd using thioglycolic acid with hydrazides, generated from the combination of hydrazides with benzaldehyde. Methods: The esters, hydrazides, hydrazones, and thiazolidines, were synthesized and characterized using infrared spectroscopy, nuclear magnetic resonance, and melting point analysis. Assessment of anti-bacterial activity was carried out against Gram-positive and Gram-negative bacterial strain of Staphylococcus aureus, Acinetobacter baumannii, Aeromonas sobria, and Escherichia coli. . Results: We synthesized ethyl 2-acetate (benzo[d]thiazol-2-yloxy), followed by the formation of 2-(benzo[d]thiazol-2-yloxy)acetohydrazide (hydrazide) through the reaction of this acetate with hydrazine.  16 compounds were synthesized with rigorous validation at each stage through spectral analysis. Thiazolidine derivatives exhibited promising inhibitory effects against bacterial growth, indicating their potential as antibacterial agents.Compound SH8 exhibited moderate to strong inhibitory effects against all tested species, notably Aeromonas sobria and Staphylococcus aureus, at a concentration of 0.1 mg/ml. Conclusion: In conclusion, the synthesized compounds exhibited both structural integrity and potent antibacterial activity, suggesting avenues for further exploration in pharmaceutical research.

Keywords:  Heterocyclic compounds, Thiazolidine derivatives, Antibacterial properties, Synthesis methods, Biological activity assessment

References

Abhinit, M., Ghodke, M., & Pratima, N. A. (2009). Exploring potential of 4-thiazolidinone: A brief review. International Journal of Pharmacy and Pharmaceutical Sciences, 1(1), 47-64.

Ahmed, S., Bhat, A. R., Rahiman, A. K., Dongre, R. S., Hasan, A. H., Niranjan, V., ... & Kawsar, S. M. (2023). Green synthesis, antibacterial and antifungal evaluation of new thiazolidine-2,4-dione derivatives: Molecular dynamic simulation, POM study and identification of antitumor pharmacophore sites. Journal of Biomolecular Structure and Dynamics, 1-17.

Al Rashidy, A. A. M., Al Badrany, K. A., & Al Garagoly, G. M. (2020, August). Spectrophotometric determination of sulphamethoxazole drug by new pyrazoline derived from 2,4-dinitrophenyl hydrazine. In Materials Science Forum (Vol. 1002, pp. 350-359). Trans Tech Publications Ltd.

Al-Hadidi, O. A. F., Al-Badrany, K. A., & Al-Bajari, S. A. (2022). Synthesis some of thiazepine compounds from 2-carbboxyaldehyde-5-methyl thiophene and study their biological activity on infected male rats epileptic. Journal of Education and Scientific Studies, 2(20).

Al-Joboury, W. M., Al-Badrany, K. A., & Asli, N. J. (2022, November). N-alkylation of substituted 2-amino benzothiazoles by 1,4-bis(bromo methyl) benzene on mixed oxides at room temperature and study their biological activity. In AIP Conference Proceedings (Vol. 2394, No. 1). AIP Publishing.

Amin, S., Sheikh, K. A., Iqubal, A., Khan, M. A., Shaquiquzzaman, M., Tasneem, S., ... & Alam, M. M. (2023). Synthesis, in-silico studies and biological evaluation of pyrimidine based thiazolidinedione derivatives as potential anti-diabetic agent. Bioorganic Chemistry, 134, 106449.

Anwar Shalan F., Samah Hussein Kadhim, (2024). Synthesis, Characterization and In Vitro Anti-cancer  Properties of Cationic Gemini Surfactants with Alkyl Chains in Human Breast Cancer, Journal of Angiotherapy, 8(1), 1-10, 9443

Apostol, I., Anghel, N., Dinu, M. V., Ziarelli, F., Mija, A., & Spiridon, I. (2023). An eco-friendly strategy for preparing lignin esters as filler in materials for removal of argan oil and sunflower oil. Reactive and Functional Polymers, 105620.

Bansal, G., Thanikachalam, P. V., Maurya, R. K., Chawla, P., & Ramamurthy, S. (2020). An overview on medicinal perspective of thiazolidine-2,4-dione: A remarkable scaffold in the treatment of type 2 diabetes. Journal of Advanced Research, 23, 163-205.

Bedair, M. A., Abuelela, A. M., Alshareef, M., Owda, M., & Eliwa, E. M. (2023). Ethyl ester/acyl hydrazide-based aromatic sulfonamides: facile synthesis, structural characterization, electrochemical measurements and theoretical studies as effective corrosion inhibitors for mild steel in 1.0 M HCl. RSC Advances, 13(1), 186-211.

Benvenutti, L., Wolff, F. R., Corrêa, T. P., Melato, J., Goldoni, F. C., De Faveri, R., ... & Quintão, N. L. M. (2023). A partial agonist of PPARγ prevents paclitaxel-induced peripheral neuropathy in mice, by inhibiting neuroinflammation. British Journal of Pharmacology.

Bi, X., Pasunooti, K. K., Lescar, J., & Liu, C. F. (2017). Thiazolidine-masked α-oxo aldehyde functionality for peptide and protein modification. Bioconjugate Chemistry, 28(2), 325-329.

Chintakunta, R., & Subbareddy, G. V. (2022). Synthesis docking studies, characterization and anti-tubercular activity of ofloxacin containing thiazolidinone derivatives. Journal of Young Pharmacists, 14(1), 77.

Doddagaddavalli, M. A., Kalalbandi, V. K. A., & Seetharamappa, J. (2023). Synthesis, characterization, crystallographic, binding, in silico and antidiabetic studies of novel 2,4-thiazolidinedione-phenothiazine molecular hybrids. Journal of Molecular Structure, 1276, 134625.

Farah M. Muhammad, Bushra A. Khairallah, K. A. Albadrany. (2024). Synthesis, characterization and Antibacterial Evaluation of Novel 1,3-Oxazepine Derivatives Using A Cycloaddition Approach, Journal of Angiotherapy, 8(3), 1-5, 9506

Hamdi, A., Yaseen, M., Ewes, W. A., Bhat, M. A., Ziedan, N. I., El-Shafey, H. W., ... & Elbadawi, M. M. (2023). Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: Design, synthesis, biological investigations, and in silico insights. Journal of Enzyme Inhibition and Medicinal Chemistry, 38(1), 2231170.

Hussein Abdulkadhim Hasan, Saad M. Mahdi, Hanaa Addai Ali. (2024). Synthesis, Charecterization, Antibacterial and Cytotoxicity of Novel Metal Complexes Derived from Azomethine Ligand (Bis Azo-Schiff Base) In Vitro and In Silico, Journal of Angiotherapy, 8(3), 1-12, 9531

Ibrahim, A. M., Shoman, M. E., Mohamed, M. F., Hayallah, A. M., & El-Din A. Abuo-Rahma, G. (2023). Chemistry and applications of functionalized 2,4-thiazolidinediones. European Journal of Organic Chemistry, 26(19), e202300184.

Katayama, H., & Morisue, S. (2017). A novel ring opening reaction of peptide N-terminal thiazolidine with 2,2′-dipyridyl disulfide (DPDS) efficient for protein chemical synthesis. Tetrahedron, 73(25), 3541-3547.

Khalid, A., Ahmed, A. A., & Wissam, M. R. (2022). Synthesis and characterization of some azetidine derivatives that derived from 6-bromo-4-fluoro-2-aminobenzothiazole and study their biological activity. Journal of Education and Scientific Studies, 2(20).

Lone, M. S., Mubarak, M. M., Nabi, S. A., Wani, F. R., Amin, S., Nabi, S., ... & Javed, K. (2023). Isonicotinoyl-butanoic acid hydrazone derivatives as anti-tubercular agents: In-silico studies, synthesis, spectral characterization and biological evaluation. Medicinal Chemistry Research, 32(5), 808-826.

Maleki, A., & Sarvary, A. (2015). Synthesis of tetrazoles via isocyanide-based reactions. RSC Advances, 5(75), 60938-60955.

Mekhlef, Y. O., AboulMagd, A. M., & Gouda, A. M. (2023). Design, synthesis, molecular docking, and biological evaluation of novel 2,3-diaryl-1,3-thiazolidine-4-one derivatives as potential anti-inflammatory and cytotoxic agents. Bioorganic Chemistry, 133, 106411.

Mohamed, S. A., Al-Badrany, K. A., & Huseen, M. S. (2022). Preparation and study of biological activity of pyrimidine compounds derived from 2-acetylpyridine. Vegueta. Anuario de la Facultad de Geografía e Historia, 22, 8.

Nasir, N. M., Alsalim, T. A., El-Arabey, A. A., & Abdalla, M. (2023). Anticancer, antioxidant activities and molecular docking study of thiazolidine-4-one and thiadiazol derivatives. Journal of Biomolecular Structure and Dynamics, 41(9), 3976-3992.

Oh, J., Patel, J., Park, H. B., & Crawford, J. M. (2018). β-Lactam biotransformations activate innate immunity. The Journal of Organic Chemistry, 83(13), 7173-7179.

Paneth, A., Kapron, B., Plech, T., Paduch, R., Trotsko, N., & Paneth, P. (2023). Combined in silico and in vitro analyses to assess the anticancer potential of thiazolidinedione–thiosemicarbazone hybrid molecules. International Journal of Molecular Sciences, 24(24), 17521.

Rita S. Adam, (2024). Synthesis and In-silico Evaluation of N-Aryl-Keto-Nitrone as a spin trapping agent in biological systems, Journal of Angiotherapy, 8(1), 1-11, 9437

Sadeek, G. T., Saeed, Z. F., & Saleh, M. Y. (2023). Synthesis and pharmacological profile of hydrazide compounds. Research Journal of Pharmacy and Technology, 16(2), 975-982.

Saleh, J. N., & Khalid, A. (2023). Synthesis, characterization and biological activity evaluation of some new pyrimidine derivatives by solid base catalyst AL2O3-OBa. Central Asian Journal of Medical and Natural Science, 4(4), 231-239.

Saleh, M. J., & Al-Badrany, K. A. (2023). Preparation, characterization of new 2-oxo pyran derivatives by AL2O3-OK solid base catalyst and biological activity evaluation. Central Asian Journal of Medical and Natural Science, 4(4), 222-230.

Sarvary, A., & Maleki, A. (2015). A review of syntheses of 1,5-disubstituted tetrazole derivatives. Molecular Diversity, 19, 189-212.

Sena, K. X., Mendes, R. F., Bôtelho, E. X., Araújo-Melo, R. O., Silva, C. J., Costa Júnior, H. N., ... & Ximenes, R. M. (2022). Antibacterial and antibiofilm activities of thiazolidine-2,4-dione and 4-thioxo-thiazolidin-2-one derivatives against multidrug-resistant Staphylococcus aureus clinical isolates. Journal of Applied Microbiology, 133(6), 3558-3572.

Shaabani, A., Maleki, A., Rezayan, A. H., & Sarvary, A. (2011). Recent progress of isocyanide-based multicomponent reactions in Iran. Molecular Diversity, 15, 41-68.

Singh, G., Kumar, R., Ds, D., Chaudhary, M., Kaur, C., & Khurrana, N. (2024). Thiazolidinedione as a promising medicinal scaffold for the treatment of type 2 diabetes. Current Diabetes Reviews, 20(6), 89-109.

Sriharsha, S. N., Jainab, N. H., Biradar, M. S., Thapa, S., Venkatesh, E. S., Bidye, D. P., ... & Dixit, S. (2023).

Wen, Y., Xie, Z., Xue, S., Long, J., Shi, W., & Liu, Y. (2023). Preparation of benzenesulfonyl hydrazone modified guar gum and its adsorption properties for dyes and phytotoxicity assays. International Journal of Biological Macromolecules, 234, 123700.