Ultrasound-Assisted One-Pot Synthesis and Anti-Inflammatory Evaluation of 2,4,5-Trisubstituted Imidazoles with Hemocompatibility Assessment

Duaa Abed Hilal; Haitham Dalol Hanoon; Narjis Hadi Al-Saadi

doi:10.22146/ijc.108494

Ultrasound-Assisted One-Pot Synthesis and Anti-Inflammatory Evaluation of 2,4,5-Trisubstituted Imidazoles with Hemocompatibility Assessment

https://doi.org/10.22146/ijc.108494

Duaa Abed Hilal^(1*), Haitham Dalol Hanoon⁽²⁾, Narjis Hadi Al-Saadi⁽³⁾

(1) Department of Chemistry, College of Science, University of Kerbala, Kerbala 56001, Iraq
(2) Department of Chemistry, College of Science, University of Kerbala, Kerbala 56001, Iraq
(3) Department of Chemistry, College of Science, University of Kerbala, Kerbala 56001, Iraq
(*) Corresponding Author

Abstract

Imidazole derivatives are well known for their anti-inflammatory potential, and recent studies focus on synthesizing 2,4,5-trisubstituted imidazoles through faster, greener methods. In the present study, a series of such derivatives (N1–N10) was prepared in a single-pot, ultrasound-assisted reaction using benzil, various aromatic aldehydes, and ammonium acetate, with sulfuric acid as the catalyst. This procedure shortens reaction times, enhances yields, and reduces waste, offering a greener alternative to conventional heating methods. The products were fully characterized by ¹H-NMR, ¹³C-NMR, FTIR, and MS. Four representative derivatives (N2, N4, N5, and N8) were selected for biological evaluation. Their anti-inflammatory activity was assessed in vitro using trypsin inhibition and albumin denaturation assays, with diclofenac sodium as the reference. N5 and N8 showed potent trypsin inhibition (61.63 ± 1.74 and 53.49 ± 0.45%) comparable to diclofenac (61.69 ± 0.74%), while N2 achieved 60.71 ± 3.68% and N4 50.33 ± 0.58%. In albumin denaturation, N5 and N8 again displayed high activity (76.8 ± 6.3 and 76.55 ± 0.89%), N2 58.33 ± 0.62% and N4 50.33 ± 0.58%. All compounds produced < 5% hemolysis, indicating good hemocompatibility. The findings demonstrate that ultrasound enables a greener and more efficient synthesis of anti-inflammatory imidazole derivatives, while also highlighting these compounds as promising, safe, and effective candidates for future therapeutic development.

Keywords

synthesis; 2,4,5-trisubstituted imidazoles; anti-inflammatory; ultrasound; hemocompatibility

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DOI: https://doi.org/10.22146/ijc.108494