Copyright (c) 2026 Nitin Jain, Dr. Usha Jain, Dadashaeb Kawade, Shweta Kale
This work is licensed under a Creative Commons Attribution 4.0 International License.
Design, Computational Study, Synthesis, Characterization and Anti-diabetic Evaluation of Novel N-Substituted Thiazolidinedione Derivatives
Corresponding Author(s) : Nitin Jain
Asian Journal of Chemistry,
Vol. 38 No. 10 (2026): Vol 38, Issue 10, 2026
Abstract
In the present study, a series of novel N-substituted 2,4-thiazolidinedione derivatives (PB-TZD1–PB-TZD14) were rationally designed, synthesized and evaluated for their antidiabetic potential. The synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR and mass spectrometry. Molecular docking revealed favourable interactions of the synthesized derivatives with key residues of the PPAR-γ receptor, particularly Cys285. In vitro glucose uptake studies revealed that PB-TZD1 (36.00%), PB-TZD3 (34.30%) and PB-TZD6 (33.53%) exhibited significantly higher activity compared to the standard drug pioglitazone (24.77%). Among these, PB-TZD3 exhibited the most pronounced glucose-lowering effect in in vivo antidiabetic studies using a high-fat diet STZ-induced rat model. Adipocyte differentiation studies showed that PB-TZD3 significantly enhanced adipogenesis at higher concentrations, consistent with PPAR-γ activation. In silico ADME and toxicity predictions suggested favourable drug-like properties; however, these findings are preliminary and require further experimental validation. The structure–activity relationship analysis indicated that electronic, steric and hydrophobic factors play a crucial role in modulating biological activity. This study identifies PB-TZD3 as a promising lead compound and highlights the significance of N-substitution in optimizing thiazolidinedione derivatives for improved antidiabetic activity.
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- G.S. Singh and Z.Y. Desta, Chem. Rev., 112, 6104 (2012); https://doi.org/10.1021/cr300135y
- F.C. Brown, Chem. Rev., 61, 463 (1961); https://doi.org/10.1021/cr60213a002
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- L.F. Tietze and U. Beifuss, Angew. Chem. Int. Ed. Engl., 32, 131 (1993); https://doi.org/10.1002/anie.199301313
- A.M. Ibrahim, M.E. Shoman, M.F.A. Mohamed, A.M. Hayallah and G.E.-D.A. Abuo-Rahma, Eur. J. Org. Chem., 26, e202300184 (2023); https://doi.org/10.1002/ejoc.202300184
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- U.N. Jain, N.P. Jain and S.V. Amrutkar, Asian J. Chem., 37, 1985 (2025); https://doi.org/10.14233/ajchem.2025.34125
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- A.J. Harte and T. Gunnlaugsson, Tetrahedron Lett., 47, 6321 (2006); https://doi.org/10.1016/j.tetlet.2006.06.090
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- I. Kaczmarek, T. Suchý, M. Strnadová and D. Thor, STAR Protoc., 5, 102977 (2024); https://doi.org/10.1016/j.xpro.2024.102977
- C. Teixeira, A.P. Sousa, I. Santos, A.C. Rocha, I. Alencastre, A.C. Pereira, D. Martins-Mendes, P. Barata, P. Baylina and R. Fernandes, Biology, 11, 806 (2022); https://doi.org/10.3390/biology11060806
References
G.S. Singh and Z.Y. Desta, Chem. Rev., 112, 6104 (2012); https://doi.org/10.1021/cr300135y
F.C. Brown, Chem. Rev., 61, 463 (1961); https://doi.org/10.1021/cr60213a002
K. Ono, A. Yoshida, N. Saito, T. Fujishima, S. Honzawa, Y. Suhara, S. Kishimoto, T. Sugiura, K. Waku, H. Takayama and A. Kittaka, J. Org. Chem., 68, 7407 (2003); https://doi.org/10.1021/jo034787y
L.F. Tietze and U. Beifuss, Angew. Chem. Int. Ed. Engl., 32, 131 (1993); https://doi.org/10.1002/anie.199301313
A.M. Ibrahim, M.E. Shoman, M.F.A. Mohamed, A.M. Hayallah and G.E.-D.A. Abuo-Rahma, Eur. J. Org. Chem., 26, e202300184 (2023); https://doi.org/10.1002/ejoc.202300184
R. Gupta, H. Joshi and C.S. Ramaa, Mini-Rev. Med. Chem., 19, 346 (2019); https://doi.org/10.2174/1389557518666171129163426
D.B. Kitchen, H. Decornez, J.R. Furr and J. Bajorath, Nat. Rev. Drug Discov., 3, 935 (2004); https://doi.org/10.1038/nrd1549
C.A. Lipinski, F. Lombardo, B.W. Dominy and P.J. Feeney, Adv. Drug Deliv. Rev., 46, 3 (2001); https://doi.org/10.1016/S0169-409X(00)00129-0
E. Lionta, G. Spyrou, D. Vassilatis and Z. Cournia, Curr. Top. Med. Chem., 14, 1923 (2014); https://doi.org/10.2174/1568026614666140929124445
U.N. Jain, N.P. Jain and S.V. Amrutkar, Asian J. Chem., 37, 1985 (2025); https://doi.org/10.14233/ajchem.2025.34125
U.N. Jain, N.P. Jain and S.V. Amrutkar, Int. J. Pharm. Qual. Assur., 15, 2455 (2024).
Y. Yang, K. Yao, M.P. Repasky, K. Leswing, R. Abel, B.K. Shoichet and S.V. Jerome, J. Chem. Theory Comput., 17, 7106 (2021); https://doi.org/10.1021/acs.jctc.1c00810
W.L. Jorgensen and E.M. Duffy, Adv. Drug Deliv. Rev., 54, 355 (2002); https://doi.org/10.1016/S0169-409X(02)00008-X
W.L. Jorgensen and E.M. Duffy, Bioorg. Med. Chem. Lett., 10, 1155 (2000); https://doi.org/10.1016/S0960-894X(00)00172-4
E.M. Duffy and W.L. Jorgensen, J. Am. Chem. Soc., 122, 2878 (2000); https://doi.org/10.1021/ja993663t
C. Lu, C. Wu, D. Ghoreishi, W. Chen, L. Wang, W. Damm, G.A. Ross, M.K. Dahlgren, E. Russell, C.D. Von Bargen, R. Abel, R.A. Friesner and E.D. Harder, J. Chem. Theory Comput., 17, 4291 (2021); https://doi.org/10.1021/acs.jctc.1c00302
G. Madhavi Sastry, M. Adzhigirey, T. Day, R. Annabhimoju and W. Sherman, J. Comput. Aided Mol. Des., 27, 221 (2013); https://doi.org/10.1007/s10822-013-9644-8
M. Wiederstein and M.J. Sippl, Nucleic Acids Res., 35(Web Server), W407 (2007); https://doi.org/10.1093/nar/gkm290
M. Shahnaz, P.K. Bhai and R. Bhai, J. Drug Deliv. Ther., 3, 96 (2013); https://doi.org/10.22270/jddt.v3i6.714
N. Long, A. Le Gresley and S.P. Wren, ChemMedChem, 16, 1716 (2021); https://doi.org/10.1002/cmdc.202100177
V. Patil, N. Upadhyay, K. Tilekar, H. Joshi and C.S. Ramaa, Iran. J. Pharm. Res., 20, 188 (2021).
A.J. Harte and T. Gunnlaugsson, Tetrahedron Lett., 47, 6321 (2006); https://doi.org/10.1016/j.tetlet.2006.06.090
G. Marc, A. Stana, A. Pîrnău, L. Vlase, S. Oniga and O. Oniga, J. Mol. Struct., 1241, 130629 (2021); https://doi.org/10.1016/j.molstruc.2021.130629
M. Gowdru Srinivasa, R. B. C, A. Prabhu, V. Rani, S.D. Ghate and P. Kumar, RSC Med. Chem., 14, 2401 (2023); https://doi.org/10.1039/D3MD00273J
N.K. Verma, J. Singh and C.S. Dey, Br. J. Pharmacol., 143, 1006 (2004); https://doi.org/10.1038/sj.bjp.0706002
I. Kaczmarek, T. Suchý, M. Strnadová and D. Thor, STAR Protoc., 5, 102977 (2024); https://doi.org/10.1016/j.xpro.2024.102977
C. Teixeira, A.P. Sousa, I. Santos, A.C. Rocha, I. Alencastre, A.C. Pereira, D. Martins-Mendes, P. Barata, P. Baylina and R. Fernandes, Biology, 11, 806 (2022); https://doi.org/10.3390/biology11060806
