Acyl hydrazides and triazoles as novel inhibitors of mammalian cathepsin B and cathepsin H

• Microwave assisted synthesis of acyl hydrazides and triazoles have been reported.
• Inhibition to endogenous proteolysis was more at 3 h as compared to 24 h.
• Inhibition type and Ki values of compounds were determined on the target enzymes.
• Differential inhibitory effect on cathepsin B and cathepsin H has been reported.
• For some compounds, Ki value of the order of 10−7 has been determined.

In the past decade, the work on the identification of small molecular weight compounds as inhibitors of cysteine proteases has been in focus. In this direction, we here present the facile microwave assisted synthesis of some acyl hydrazides and triazoles, followed by their evaluation as protease inhibitors and inhibitory studies on cathepsin B and cathepsin H, two significant lysosomal cysteine proteases. The compounds were characterized by 1H NMR, 13C NMR, Mass and IR spectral data. The compounds which were found inhibitory to endogenous proteolysis in liver homogenate at pH 5.0 were further studied for determination of inhibition type and Ki values on purified cathepsin B and cathepsin H. The maximum inhibitory effect was exerted by 3-(3′-nitrophenyl)-5-(3′-nitrophenyl)-4-amino-1,2,4-triazoles (2c), 3-(4′-chlorophenyl)-5-(4′-chloro phenyl)-4-amino-1,2,4-triazoles (2h), 3-(3′-aminophenyl)-5-(3′-aminophenyl)-4-amino-1,2,4-triazoles (2i) and 4-methoxybenzohydrazide (1b).

Acyl hydrazides and 4-amino-1,2,4-triazoles were synthesized under microwave conditions. The maximum inhibitory effect on cathepsin B and cathepsin H was exerted by compounds (2c), (2h), (2i) and (1b).Figure optionsDownload as PowerPoint slide