We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×

Synthesis, biological evaluation and in silico studies of some new analogues of 3,5-vdisubstituted thiazolidin-2,4-dione

    Harsh Kumar

    Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India

    Vaish Institute of Pharmaceutical Education and Research, Rohtak, 124001, India

    ,
    Aastha Sharma

    Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India

    ,
    Davinder Kumar

    Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India

    ,
    Minakshi Gupta Marwaha

    Department of Pharmaceutical Sciences, Sat Priya College of Pharmacy, Rohtak, 124001, India

    ,
    Meenakshi Dhanawat

    Àmity institute of Pharmacy, Amity University Haryana, Gurugram, 122105, India

    ,
    Navidha Aggarwal

    *Author for correspondence:

    E-mail Address: navidhabansal16@gmail.com

    MM College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, India

    &
    Rakesh Kumar Marwaha

    **Author for correspondence:

    E-mail Address: rkmarwaha.mdu@gmail.com

    Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India

    Published Online:https://doi.org/10.4155/fmc-2023-0237

    Background: A new series of 3,5-disubstituted thiazolidin-2,4-dione molecules were derived and characterized using various spectral techniques (1H NMR, IR, carbon, hydrogen, nitrogen, etc.) and physicochemical parameters. Materials & methods: The molecules were derived using Knoevenagel condensation followed by Mannich reaction and further synthesized analogues were screened for their antioxidant and antimicrobial potential using 2,2-diphenyl-1-picrylhydrazyl free radical scavenging method and serial tube dilution method, respectively, along with in silico studies (docking and absorption, distribution, metabolism and excretion parameters) to explore the drug–receptor interaction and druglikeness. Results & conclusion: In antimicrobial screening, the analogs MP2, MM6, MM7 and MM8 displayed promising activity while molecule MM4 exhibited better antioxidant potential in the series. In molecular docking analysis, the best-fitted analogs, namely, MM6 and MM7, showed good interactions.

    Graphical abstract

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1. Parekh NM, Juddhawala KV, Rawal BM. Antimicrobial activity of thiazolyl benzene sulfonamide-condensed 2,4-thiazolidinediones derivatives. Med. Chem. Res. 22, 2737–2745 (2012).
    • 2. Trotsko N, Kosikowska U, Paneth A, Plech T, Malm A, Wujec M. Synthesis and antibacterial activity of new thiazolidine-2,4-dione-based chlorophenyl thiosemicarbazone hybrids. Molecules 23, 1023 (2018).
    • 3. Kumar H, Aggarwal N, Marwaha MG et al. Thiazolidin-2,4-dione scaffold: an insight into recent advances as antimicrobial, antioxidant, and hypoglycemic agents. Molecules 27, 6763 (2022).
    • 4. Fettach S, Thari FZ, Hafidi Z et al. Biological, toxicological and molecular docking evaluations of isoxazoline-thiazolidine-2,4-dione analogues as new class of anti-hyperglycemic agents. J. Biomol. Struct. Dyn. 41(3), 1072–1084 (2023).
    • 5. Mohd Siddique MU, Thakur A, Shilkar D et al. Non-carboxylic acid inhibitors of aldose reductase based on N-substituted thiazolidinedione derivatives. Eur. J. Med. Chem. 223, 113630 (2021).
    • 6. Jiang B, Luo J, Guo S, Wang L. Discovery of 5-(3-bromo-2-(2,3-dibromo-4,5-dimethoxybenzyl)-4,5-dimethoxybenzylidene)thiazolidine-2,4-dione as a novel potent protein tyrosine phosphatase 1B inhibitor with antidiabetic properties. Bioorg. Chem. 108, 104648 (2021).
    • 7. Aziz HA, El-Saghier AMM, Badr M, Abuo-Rahma GEDA, Shoman ME. Thiazolidine-2,4-dione-linked ciprofloxacin derivatives with broad-spectrum antibacterial, MRSA and topoisomerase inhibitory activities. Mol. Divers. 26, 1743–1759 (2022).
    • 8. Akhavan M, Foroughifar N, Pasdar H, Bekhradnia A. Green synthesis, biological activity evaluation, and molecular docking studies of aryl alkylidene 2, 4-thiazolidinedione and rhodanine derivatives as antimicrobial agents. Comb. Chem. High Throughput Screen. 22, 716–727 (2019).
    • 9. Sethi NS, Prasad DN, Singh RK. Synthesis, anticancer, and antibacterial studies of benzylidene bearing 5-substituted and 3,5-disubstituted-2,4-thiazolidinedione derivatives. Med. Chem. 17, 369–379 (2021).
    • 10. Abdelgawad MA, El-Adl K, El-Hddad SSA et al. Design, molecular docking, synthesis, anticancer and anti-hyperglycemic assessments of thiazolidine-2,4-diones bearing sulfonylthiourea moieties as potent VEGFR-2 inhibitors and PPAR agonists. Pharmaceuticals (Basel) 15, 226 (2022).
    • 11. Taghour MS, Elkady H, Eldehna WM et al. Design and synthesis of thiazolidine-2,4-diones hybrids with 1,2-dihydroquinolones and 2-oxindoles as potential VEGFR-2 inhibitors: in vitro anticancer evaluation and in silico studies. J. Enzym. Inhib. Med. Chem. 37, 1903–1917 (2022).
    • 12. Ibrahim HS, Abdelsalam M, Zeyn Y et al. Synthesis, molecular docking and biological characterization of pyrazine linked 2-aminobenzamides as new class I selective histone deacetylase (HDAC) inhibitors with anti-leukemic activity. Int. J. Mol. Sci. 23, 369 (2022).
    • 13. Yu I, Choi D, Lee HK, Cho H. Synthesis, and biological evaluation of new benzylidenethiazolidine-2,4-dione derivatives as 15-hydroxyprostaglandin dehydrogenase inhibitors to control the intracellular levels of prostaglandin E2 for wound healing. Biotechnol. Bioprocess. Eng. 24, 464–475 (2019).
    • 14. Trotsko N, Golus J, Kazimierczak P et al. Synthesis and antimycobacterial activity of thiazolidine-2,4-dione based derivatives with halogenbenzohydrazones and pyridinecarbohydrazones substituents. Eur. J. Med. Chem. 189, 112045 (2020).
    • 15. Ratnaparkhi H, Thakar S, Bansode D. An overview of chemistry and antitubercular activity of thiazolidinediones. Sch. Acad. J. Pharm. 9, 23–31 (2020).
    • 16. Elkamhawy A, Kim NY, Hassan AHE. Thiazolidine-2,4-dione-based irreversible allosteric IKK-β kinase inhibitors: optimization into in vivo active anti-inflammatory agents. Eur. J. Med. Chem. 188, 111955 (2020).
    • 17. Abdellatif KRA, Fadaly WAA, Kamel GM, Elshaier YAMM, El-Magd MA. Design, synthesis, modeling studies and biological evaluation of thiazolidine derivatives containing pyrazole core as potential anti-diabetic PPAR-γ agonists and anti-inflammatory COX-2 selective inhibitors. Bioorg. Chem. 82, 86–99 (2019).
    • 18. Asati V, Bajaj S, Mahapatra DK, Bharti SK. Molecular modeling studies of some thiazolidine-2,4-dione derivatives as 15-PGDH inhibitors. Med. Chem. Res. 25, 94–108 (2015).
    • 19. Sharma RK, Younis Y, Mugumbate G et al. Synthesis and structure activity-relationship studies of thiazolidinediones as antiplasmodial inhibitors of the Plasmodium falciparum cysteine protease falcipain-2. Eur. J. Med. Chem. 90, 507–518 (2015).
    • 20. Ahmadi A, Khalili M, Sohrabi L, Delzendeh N, Nahri-Niknafs B, Ansari F. Synthesis and evaluation of the hypoglycemic and hypolipidemic activity of sulfonamide-benzothiazole derivatives of benzylidene-2,4-thiazolidnedione. Mini Rev. Med. Chem. 17, 721–726 (2017).
    • 21. Mohammed-Iqbal AK, Khan AY, Kalashetti MB, Belavagi NS, Gong YD, Khazi IAM. Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring. Eur. J. Med. Chem. 53, 308–315 (2012).
    • 22. Tanaka T, Okuyama-Dobashi K, Motohashi R et al. Inhibitory effect of a novel thiazolidinedione derivative on hepatitis B virus entry. Antiviral Res. 194, 105165 (2021).
    • 23. Bahare RS, Ganguly S, Choowongkomon K, Seetaha S. Synthesis, HIV-1 RT inhibitory, antibacterial, antifungal and binding mode studies of some novel N-substituted 5-benzylidine-2,4-thiazolidinediones. DARU J. Pharm. Sci. 23, 6 (2015).
    • 24. Sameeh MY, Khowdiary MM, Nassar HS, Abdelall MM, Alderhami SA, Elhenawy AA. Discovery potent of thiazolidinedione derivatives as antioxidant, α-amylase inhibitor and antidiabetic agent. Biomedicines 10, 24 (2022).
    • 25. Kumar H, Deep A, Marwaha RK. Design, synthesis, in silico studies and biological evaluation of 5-((E)-4-((E)-(substituted aryl/alkyl)methyl)benzylidene) thiazolidine-2,4-dione derivatives. BMC Chem. 14, 25 (2020). •• This article is a continuation of the work from this reference.
    • 26. Kumar H, Kumar D, Kumar P et al. Synthesis, biological evaluation and in silico ADME studies of novel series of thiazolidin-2,4-dione derivatives as antimicrobial, antioxidant and anticancer agents. BMC Chem. 16, 68 (2022). •• This article is a continuation of the work from this reference.
    • 27. Serban G, Stanasel O, Serban E, Bota S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Des. Devel. Ther. 12, 1545–1566 (2018).
    • 28. Moorthy P, Ekambaram SP, Perumal SS. Synthesis, characterization and antimicrobial evaluation of imidazolyl thiazolidinedione derivatives. Arab. J. Chem. 12, 413–419 (2019).
    • 29. Goel A, Garima, Aggarwal N et al. Skin and soft tissue infections: current advancement in epidemiology, pathogenesis and management. J. Pure Appl. Microbiol. 17(1), 89–111 (2023).
    • 30. Sharma D, Kumar S, Narasimhan B et al. Synthesis, molecular modelling and biological significance of N-(4-(4-bromophenyl) thiazol-2-yl)-2-chloroacetamide derivatives as prospective antimicrobial and antiproliferative agents. BMC Chem. 13, 46 (2019).
    • 31. Aggarwal N, Jain S. A synthetic approach, characterization and biological evaluation of novel 5-(arylidene)-2-(5-methyl-1,3,4-thiadiazol-2-ylimino) thiazolidin-4-one derivatives. Asian J. Chem. 33, 1530–1536 (2021).
    • 32. Makie SJ, Neuman KC, Maxwell A. DNA topoisomerases: advances in understanding of cellular roles and multi-protein complexes via structure-function analysis. BioEssays 43, 1–19 (2021).
    • 33. Perumal P, Pandey VP, Parasuraman P. Docking studies on some novel piperidine analogues against DNA gyrase enzyme. Inventi Rapid Molecular Modeling 1, 1–4 (2014).
    • 34. Ibrahim TS, Almalki AJ, Moustafa AH et al. Novel 1,2,4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: design, synthesis, ADMET prediction and molecular docking study. Bioorg. Chem. 111, 104885 (2021).
    • 35. Marc G, Araniciu C, Oniga SD et al. Design, synthesis and biological evaluation of new piperazin-4-yl-(acetyl-thiazolidine-2,4-dione) norfloxacin analogues as antimicrobial agents. Molecules 24(21), 3959 (2019).
    • 36. Ponnusamy T, Alagumuthu M, Thamaraiselvi S. Drug efficacy of novel 3-O-methoxy-4-halo disubstituted 5,7-dimethoxy chromans; evaluated via DNA gyrase inhibition, bacterial cell wall lesion and antibacterial prospective. Bioorg. Med. Chem. 26(12), 3438–3452 (2018).
    • 37. Durcik M, Tammela P, Barancokova M et al. Synthesis and evaluation of N-phenylpyrrolamides as DNA gyrase B inhibitors. ChemMedChem 13(2), 186–198 (2018).
    • 38. Ho SY, Wang W, Ng FM et al. Discovery of dual GyrB/ParE inhibitors active against Gram-negative bacteria. Eur. J. Med. Chem. 157, 610–621 (2018).
    • 39. Abu-Melha S. Synthesis and biological evaluation of some novel 1,8-naphthyridine derivatives. Acta Chim. Slov. 64(4), 919–930 (2017).
    • 40. Wang J, Urban L. The impact of early ADME profiling on drug discovery and development strategy. Drug Discov. World Fall 5, 73–86 (2004).
    • 41. Wang J, Urban L, Bojanic D. Maximising use of in vitro ADMET tools to predict in vivo bioavailability and safety. Expert Opin. Drug Metab. Toxicol. 3, 641–665 (2007).
    • 42. Sharma D, Kumar S, Narasimhan B et al. 4-(4-Bromophenyl)-thiazol-2-amine derivatives: synthesis, biological activity and molecular docking study with ADME profile. BMC Chem. 13, 60 (2019).
    • 43. Wu F, Zhou Y, Li L et al. Computational approaches in preclinical studies on drug discovery and development. Front. Chem. 8, 726 (2020).
    • 44. Nkurunziza JB, Dukuziyaturemye P, Musabwa E, Kalluraya B. Facile synthesis, characterization and in silico docking studies of novel thiazolidine-2,4-dione-based Mannich base bearing furan/thiophene moiety as promising anti-inflammatory agents. Rwanda J. Eng. Sci. Technol. Environ. 4, 1–17 (2021). • Aided in the selection of proteins from Protein Data Bank for docking.
    • 45. Cappuccino JC, Sherman N. Microbiology – A Laboratory Manual. Addison Wesley, CA, USA (1999). • Provided method of antibacteial activity.
    • 46. The Indian Pharmacopoeia Commission. Pharmacopoeia of India (Volume 1). Controller of Publication, Ministry of Health Department, Government of India, New Delhi, India, 37 (2007). • Provided the nutrient media(s) composition.
    • 47. Koppireddi S, Komsani JR, Avula S et al. Novel 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides as antioxidant and/or anti-inflammatory compounds. Eur. J. Med. Chem. 66, 305–313 (2013). • Provided the method for antioxidant activity.
    • 48. Jas MJS, Marimuthu G, Prithivirajan B. Hydrazone analogues: molecular modeling, synthesis, in-vivo anti-nociceptive activity and in vitro antimicrobial activity. Egypt. J. Chem. 62, 1441–1450 (2019).
    • 49. Singh J, Kumar M, Mansuri R, Sahoo GC, Deep A. Inhibitor designing, virtual screening and docking studies for methyltrans-ferase: a potential target against dengue virus. J. Pharm. Bioallied Sci. 8, 188–194 (2016).
    • 50. Koehler MFT, Bergeron P, Blackwood EM, Bowman K et al. Development of a potent, specific CDK8 kinase inhibitor which phenocopies CDK8/19 knockout cells. ACS Med. Chem. Lett. 7, 223–228 (2016).
    • 51. Goel A, Aggarwal N, Jain S. Novel methodology for synthesis and computational analysis of zinc complexes of isatin derivatives and screening their biological activity. Antiinfect. Agents 20(5), 46–55 (2022).
    • 52. Xi M, Chen T, Wu C et al. CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors. Eur. J. Med. Chem. 164, 77–91 (2019).
    • 53. Gleeson MP, Hersey A, Hannongbua S. In silico ADME models: a general assessment of their utility in drug discovery applications. Curr. Top. Med. Chem. 11, 358–381 (2011).
    • 54. Wang JC. Untangling the Double Helix: DNA Entanglement and the Action of the DNA Topoisomerases. Cold Spring Harbor, NY, USA (2009).
    • 55. Arevalo JMC, Amorim JC. Virtual screening, optimization and molecular dynamics analyses highlighting a pyrrolo[1,2-a] quinazoline derivative as a potential inhibitor of DNA gyrase B of Mycobacterium tuberculosis. Sci. Rep. 12, 4742 (2022).
    • 56. Maxwell A, Lawson DM. The ATP binding site of type II topoisomerases as a target for antibacterial drugs. Curr. Top. Med. Chem. 3, 283–303 (2003). • Aided in the selection of protein for docking.