Synthesis, Characterisation and Urease Inhibitory Evaluation of Novel 1,2,4-Triazole Derivatives

Venkatesh D

doi:10.46796/ijpc.v7i2.969

D. Venkatesh Department of Chemistry, Quli Qutub Shah Government Polytechnic, Hyderabad -500064, Telangana, India.

DOI https://doi.org/10.46796/ijpc.v7i2.969

Abstract

Urease is a nickel-dependent enzyme involved in several clinically important urease-associated disorders, making inhibition of this enzyme an attractive approach for developing new bioactive compounds. The 1,2,4-triazole scaffold provides a versatile platform for structural modification and enzyme-inhibitory activity. The present study aimed to synthesize, characterize and evaluate a series of novel S-substituted 1,2,4-triazole derivatives (TRZ-1–TRZ-8) for urease inhibitory activity. Methods: The derivatives were synthesized through a multistep route involving benzohydrazide, potassium benzoyldithiocarbazate and 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol, followed by S-alkylation with substituted benzyl halides. The compounds were characterized by TLC, FTIR, ¹H NMR and mass spectrometric analysis. Urease inhibition was evaluated by a phenol–hypochlorite colorimetric method, with thiourea as the reference inhibitor. Results: At 100 µM, the derivatives produced 45.8–76.8% urease inhibition, with TRZ-6 (4-Cl) showing the highest inhibition (76.8 ± 1.7%). TRZ-6 exhibited concentration-dependent activity and an IC₅₀ of 44.6 µM, followed by TRZ-7 (50.9 µM) and TRZ-5 (58.3 µM), whereas thiourea showed an IC₅₀ of 26.4 µM. Conclusion: The findings indicate that substitution of the 1,2,4-triazole scaffold influenced urease inhibitory activity, with the 4-chloro derivative TRZ-6 showing the strongest activity among the synthesized compounds. These results support further optimization and biological investigation of substituted 1,2,4-triazoles as potential urease inhibitors.

Keywords: 1,2,4-Triazole, urease inhibition, TRZ-6, thiourea, heterocyclic synthesis, molecular docking, structure–activity relationship

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