title: Acyl hydrazides and triazoles as novel inhibitors of mammalian cathepsin B and cathepsin H.
abstract: 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 (1)H NMR, (13)C 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).
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India. Electronic address: nraghav.chem@gmail.com.
authors.forename: Neera
authors.initials: N
authors.lastname: Raghav
authors.affiliation: Department of Chemistry, Kurukshetra University, Kurukshetra, 136119, India.
authors.forename: Mamta
authors.initials: M
authors.lastname: Singh
mesh_terms: D000818:Animals; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056655:Cathepsin H / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006041:Goats; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D006834:Hydrazines; D011480:Protease Inhibitors; D014230:Triazoles; D002401:Cathepsin B; D056655:Cathepsin H
keywords: 4-Amino-1,2,4-triazoles; Acyl hydrazides; Cathepsin B inhibitors; Cathepsin H inhibitors; Endogenous proteolysis