Abstract
This work reports a novel and highly efficient methodology for the synthesis of Schiff bases of 4-amino-1,2,4-triazole derivatives (3a-h) by the condensation of 4-amino-5-methyl-3-oxo-2-tosyl-1,2,4-triazol-3-one (2) derivative with various aromatic aldehydes under ultrasound irradiation. The major advantages of the reported method are its operational simplicity, extremely mild reaction conditions, short reaction times, and excellent yields. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, elemental analysis, and the X-ray crystallography (for compound 3f).
The antioxidant activity of the synthesized compounds was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method. The IC50 value of synthesized Schiff bases were calculated and compared with standard BHA. All compounds showed excellent activity with inhibition values in the range of 71.22 ± 0.98–96.42 ± 0.02% at 1.20 μM.
The newly synthesized compounds were also evaluated for angiotensin I-converting enzyme (ACE) inhibition. The results were compared to captopril as a reference drug. All compounds showed ACE inhibition activity from 66% to 95%. Moreover, the synthetic compounds displayed virtually no cytotoxicity. The docking of chemical compounds in the ACE active site revealed possible inhibitory effect of all compounds on the catalytic activity of the enzyme, which would satisfactorily explain the anti-hypertensive effect of these compounds.
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•A series of Schiff bases of 4-amino-1,2,4-triazole derivatives under ultrasound irradiation were synthesized.•Ultrasound irradiation method was more efficient than conventional thermal heating.•All the synthesized compounds (3a–h) exhibited antioxidant properties.•The Schiff bases have shown significant inhibitory action against ACE.•The molecular modelling of the tested compounds to angiotensin I-converting enzyme was investigated.