A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies

Semiha Köprü

doi:10.17798/bitlisfen.1844808

A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies

Abstract

In the present study, new multifunctional imidazoles which contains the synthesis and biological activity experiments have been reported as α-glucosidase inhibitors. The procedure of imidazole-hydrazone derivative compounds (ISA1-5) relies on the condensation reaction of 5-Cl isatin and 2-benzylidenehydrazinecarboximidamide compounds. Bioactivity evaluation results revealed that among the imidazole-based hydrazones, ISA-3 with a 4-F substitution (IC50=28.88 and µM) and ISA-4 with a 4-methyl substitution (IC50=27.73 µM) were observed to have better α-glucosidase inhibition than the reference compound, acarbose. Molecular docking studies were performed against the 3A4A protein to predict how the synthesized derivatives bind to the target enzyme. In conclusion, the data obtained were consistent with in vitro results and also determined that imidazole hydrazones are antidiabetic agents.

Keywords

Ethical Statement

The study is complied with research and publication ethics.

Thanks

The author is thank to Erciyes University Technology Research and Application Center to the laboratory for the FT-IR and NMR analyses. Thanks to Prof. Dr. Şevki Adem for α-glucosidase activity studies.

References

I. Heydari, V. Radi, S. Razmjou, and A. Amiri, “Chronic complications of diabetes mellitus in newly diagnosed patients,” International Journal of Diabetes Mellitus, vol. 2, no. 1, pp. 61–63, Apr. 2010, doi: 10.1016/j.ijdm.2009.08.001.
V. Pogaku, K. Gangarapu, S. Basavoju, K. K. Tatapudi, and S. B. Katragadda, “Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors,” Bioorganic Chemistry, vol. 93, p. 103307, Dec. 2019, doi: 10.1016/j.bioorg.2019.103307.
S. Daud et al., “Isatin-based ibuprofen and mefenamic acid Schiff base derivatives as dual inhibitors against urease and α–glucosidase: In vitro, in silico and cytotoxicity studies,” Journal of Saudi Chemical Society, vol. 28, no. 5, p. 101905, Sep. 2024, doi: 10.1016/j.jscs.2024.101905.
M. I. Tousif et al., “Phenolics from endophytic fungi as natural α-glucosidase inhibitors: A comprehensive review,” Journal of Molecular Structure, vol. 1291, p. 135852, Nov. 2023, doi: 10.1016/j.molstruc.2023.135852.
L. Zhang, X.-M. Peng, G. L. V. Damu, R.-X. Geng, and C.-H. Zhou, “Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry,” Medicinal Research Reviews, vol. 34, no. 2, pp. 340–437, Jun. 2013, doi: 10.1002/med.21290.
G. Yadav and R. Jain, “An insight into Synthetic, Structural and Medicinal perspective of imidazole analogs: A review,” European Journal of Medicinal Chemistry, vol. 290, p. 117524, Jun. 2025, doi: 10.1016/j.ejmech.2025.117524.
S. Poyraz, M. Yıldırım, and M. Ersatir, “Recent pharmacological insights about imidazole hybrids: a comprehensive review,” Medicinal Chemistry Research, vol. 33, no. 6, pp. 839–868, May 2024, doi: 10.1007/s00044-024-03230-2.
P. Vennila et al., “Synthesis, spectroscopic characterization, molecular docking studies and DFT calculation of novel Mannich base 1-((4-ethylpiperazin-1-yl)(2-hydroxyphenyl)methyl)naphthalen-2-ol,” Journal of Molecular Structure, vol. 1246, p. 131164, Dec. 2021, doi: 10.1016/j.molstruc.2021.131164.

V. O. Golfarb-Abramov et al., “Synthesis, structure investigation and evaluation of anti-orthopoxvirus activities of 2-(2-arylethenyl)imidazoles,” New Journal of Chemistry, vol. 49, no. 45, pp. 19699–19717, 2025, doi: 10.1039/d5nj03203b.
A. Ghara, G. S. P. Matada, P. Pramanick, U. R. Sharma, B. Metikurki, and P. S. Dhiwar, “Exploring the molecular insights of imidazole and benzimidazole scaffold for cancer therapy: Synthesis, in-vitro cytotoxicity and SAR studies,” Journal of Molecular Structure, vol. 1322, p. 140324, Feb. 2025, doi: 10.1016/j.molstruc.2024.140324.
Z. R. Banoon, R. S. Mahmood, A. R. Hamad, and Z. A. Hussein, “Design, microwave synthesis, characterization and antimicrobial activity of imidazolone derivatives,” Journal of Molecular Structure, vol. 1322, p. 140701, Feb. 2025, doi: 10.1016/j.molstruc.2024.140701.
D. Satheesh, A. Rajendran, C. Geetha, K. Parthipan, A. Thirunavukkarasu, and K. Suganya, “Anti-inflammatory and anti-diabetic activity of N1-(4-substitutedbenzyl)/Butyl-2-methyl-4-nitro-3-imidazolium (E)-3-(4-hydroxy-3-methoxyphenyl)acrylates,” Journal of Ionic Liquids, vol. 5, no. 1, p. 100148, Jun. 2025, doi: 10.1016/j.jil.2025.100148.
B. S. Daisylet, S. J. Raphael, P. P. Rajan, A. Mohan, P. Kumar, and A. Dasan, “Evaluation of photocatalytic, biological, and antidiabetic activities of benzimidazole-based metal complexes derived from o-phenylenediamine and imidazole-2-carboxaldehyde,” Inorganic Chemistry Communications, vol. 180, p. 114951, Oct. 2025, doi: 10.1016/j.inoche.2025.114951.
S. K. Pathan et al., “Exploring antibiofilm potential of some new imidazole analogs against C. albicans: synthesis, antifungal activity, molecular docking and molecular dynamics studies,” Journal of Biomolecular Structure and Dynamics, vol. 43, no. 6, pp. 3099–3115, Jan. 2024, doi: 10.1080/07391102.2023.2296604.
C. B. Dhurjad, S. Sharma, R. A. Shinde, A. Y. A. Alzahrani, and V. A. Adole, “Synthesis, computational and biological evaluation of imidazole-pyrazole hydrazones as antitubercular agents,” Journal of Molecular Structure, vol. 1353, p. 144667, Feb. 2026, doi: 10.1016/j.molstruc.2025.144667.
M. Faris et al., “Imidazole-Derived Alkyl and Aryl Ethers: Synthesis, Characterization, In Vitro Anticancer and Antioxidant Activities, Carbonic Anhydrase I–II Inhibition Properties, and In Silico Studies,” ACS Omega, vol. 9, no. 19, pp. 20937–20956, May 2024, doi: 10.1021/acsomega.4c00028.
A. A. Amer, N. Al‐Hoshani, M. A. Gad, and A. A. Abdelhamid, “Exploring the Biodiversity of Substituted Imidazole: Novel Synthetic Strategy of Polysubstituted Imidazole as Insecticidal and Antibacterial Agents,” Chemistry & Biodiversity, Aug. 2025, doi: 10.1002/cbdv.202500839.
M. Yar et al., “Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes,” Bioorganic Chemistry, vol. 58, pp. 65–71, Feb. 2015, doi: 10.1016/j.bioorg.2014.11.006.
P. Kumar et al., “Synthesis, Biological Evaluation, Molecular Docking and Kinetic Investigation of New 2,4,5‐Trisubstituted Imidazole Derivatives as Antidiabetic Agents,” ChemistrySelect, vol. 8, no. 31, Aug. 2023, doi: 10.1002/slct.202300924.
B. Narasimhan, D. Sharma, and P. Kumar, “Biological importance of imidazole nucleus in the new millennium,” Medicinal Chemistry Research, vol. 20, no. 8, pp. 1119–1140, Nov. 2010, doi: 10.1007/s00044-010-9472-5.
S. Charan et al., “Anticancer activity of hydrazones in the last quinquennial period: A special emphasis on various enzyme targets and SAR,” European Journal of Medicinal Chemistry, vol. 302, p. 118305, Jan. 2026, doi: 10.1016/j.ejmech.2025.118305.
Shaveta, S. Mishra, and P. Singh, “Hybrid molecules: The privileged scaffolds for various pharmaceuticals,” European Journal of Medicinal Chemistry, vol. 124, pp. 500–536, Nov. 2016, doi: 10.1016/j.ejmech.2016.08.039.
M. Khalfaoui et al., “Design, synthesis, and comprehensive evaluation of novel imidazole–chromone hybrids as potent cholinesterase and α-glucosidase inhibitors,” European Journal of Medicinal Chemistry, vol. 297, p. 117927, Nov. 2025, doi: 10.1016/j.ejmech.2025.117927.
I. A. S. Al-Janabi et al., “Antiproliferative activity and molecular docking studies of new 4-oxothiazolidin-5-ylidene acetate derivatives containing guanylhydrazone moiety,” Journal of Molecular Structure, vol. 1258, p. 132627, Jun. 2022, doi: 10.1016/j.molstruc.2022.132627.
M. Tapera et al., “Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular docking studies of new imidazolyl hydrazone derivatives,” Journal of Molecular Structure, vol. 1269, p. 133816, Dec. 2022, doi: 10.1016/j.molstruc.2022.133816.
H. Kashtoh et al., “Oxadiazoles and thiadiazoles: Novel α-glucosidase inhibitors,” Bioorganic & Medicinal Chemistry, vol. 22, no. 19, pp. 5454–5465, Oct. 2014, doi: 10.1016/j.bmc.2014.07.032.
B. S. Kurşun‐Aktar, Ş. Adem, G. Tatar‐Yilmaz, Z. A. H. Hameed, and E. E. Oruç‐Emre, “Investigation of α‐glucosidase and α‐amylase inhibitory effects of phenoxy chalcones and molecular modeling studies,” Journal of Molecular Recognition, vol. 36, no. 11, Sep. 2023, doi: 10.1002/jmr.3061.
S. Kopru, “Novel Schiff’s and N-Mannich base derivatives of isatin: Synthesis, spectroscopic characterization, molecular docking, dft studies, in vitro cholinesterase enzyme inhibition and antioxidant properties,” Journal of Molecular Structure, vol. 1350, p. 143949, Jan. 2026, doi: 10.1016/j.molstruc.2025.143949.
D. F. Veber, S. R. Johnson, H.-Y. Cheng, B. R. Smith, K. W. Ward, and K. D. Kopple, “Molecular Properties That Influence the Oral Bioavailability of Drug Candidates,” Journal of Medicinal Chemistry, vol. 45, no. 12, pp. 2615–2623, May 2002, doi: 10.1021/jm020017n.
C. Zhang et al., “Molecular docking technology drives multidimensional applications of microbial natural products,” Journal of Molecular Structure, vol. 1335, p. 142044, Jul. 2025, doi: 10.1016/j.molstruc.2025.142044.
O. Trott and A. J. Olson, “AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading,” Journal of Computational Chemistry, vol. 31, no. 2, pp. 455–461, Jun. 2009, doi: 10.1002/jcc.21334.
Dassault Systèmes BIOVIA, Discovery Studio Modeling Environment, Release 2020. Dassault Systèmes, 2020.
J. Liu, J. Niu, L. Xu, and H. Zhao, “Identification of Novel Neuraminidase Inhibitors as Potential Anti-Influenza Agents: Virtual Screening, Molecular Docking, in vitro Validation and Molecular Dynamic Simulation Studies,” Cell Biochemistry and Biophysics, vol. 83, no. 3, pp. 3535–3546, Mar. 2025, doi: 10.1007/s12013-025-01734-1.

Details

Primary Language

English

Subjects

Organic Chemical Synthesis

Journal Section

Research Article

Authors

Semiha Köprü ^*
0000-0002-2269-6980
Türkiye

Publication Date

September 30, 2026

Submission Date

December 18, 2025

Acceptance Date

July 17, 2026

Published in Issue

Year 2026 Volume: 15 Number: 3

DOI

https://doi.org/10.17798/bitlisfen.1844808

IZ

https://izlik.org/JA23DZ89RC

Cite

RIS / Bibtex

APA

Köprü, S. (2026). A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, 15(3), 1069-1081. https://doi.org/10.17798/bitlisfen.1844808

AMA

1.Köprü S. A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi. 2026;15(3):1069-1081. doi:10.17798/bitlisfen.1844808

Chicago

Köprü, Semiha. 2026. “A New Series of Imidazole Based Hydrazones As Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies”. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 15 (3): 1069-81. https://doi.org/10.17798/bitlisfen.1844808.

EndNote

Köprü S (September 1, 2026) A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 15 3 1069–1081.

IEEE

[1]S. Köprü, “A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies”, Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, vol. 15, no. 3, pp. 1069–1081, Sept. 2026, doi: 10.17798/bitlisfen.1844808.

ISNAD

Köprü, Semiha. “A New Series of Imidazole Based Hydrazones As Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies”. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi 15/3 (September 1, 2026): 1069-1081. https://doi.org/10.17798/bitlisfen.1844808.

JAMA

1.Köprü S. A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi. 2026;15:1069–1081.

MLA

Köprü, Semiha. “A New Series of Imidazole Based Hydrazones As Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies”. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi, vol. 15, no. 3, Sept. 2026, pp. 1069-81, doi:10.17798/bitlisfen.1844808.

Vancouver

1.Semiha Köprü. A New Series of Imidazole Based Hydrazones as Potent Anti-Diabetic Agents: Synthesis, In Vitro α-Glucosidase Inhibition and Molecular Docking Studies. Bitlis Eren Üniversitesi Fen Bilimleri Dergisi. 2026 Sep. 1;15(3):1069-81. doi:10.17798/bitlisfen.1844808