In-vitro Inhibition Studies on Endogenous Proteolysis of Liver Homogenate in Presence of Synthesized Pyrazoles
نویسندگان
چکیده
Objective: Pyrazoles have wide application in medicinal chemistry because of diverse pharmacological activities. As a part of our ongoing research to identify potential inhibitors of cysteine proteases, these observations were guiding initiatives in the present work for the synthesis of some pyrazoles with a desire to see their inhibitory effect on endogenous proteolysis. Methods: We have synthesized a series of substituted pyrazoles by hypervalent iodine oxidation of 1, 3, 5-triphenyl pyrazolines which were obtained from the reaction of the corresponding chalcones with phenyl hydrazines. The structure of the compounds was confirmed on the basis of IR & 1H-NMR spectrum. The acid soluble proteins were quantitated in the supernatant using Bradford method. Results: In the present work, we have demonstrated in-vitro effects of substituted pyrazoles on endogenous proteolysis in liver homogenate. It was observed that 5-(-4’-methylphenyl)-1,3-diphenyl-2-pyrazole (1g) in 3 hr reaction and 5-(-4’-fluorophenyl)-1,3-diphenyl-2-pyrazole (1e) in 24 hr reaction showed more inhibition while unsubstituted 1, 3, 5triphenyl-2-pyrazole (1a) showed high inhibition both is 3 and 24 hr incubation. Conclusion: These compounds act as inhibitors to proteases active at pH 5.0, and inhibit endogenous protein hydrolysis significantly. In general, some compounds demonstrated ~100% inhibition at 1mM concentration.
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تاریخ انتشار 2013