Skip to Content
MilliporeSigma
  • Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3.

Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3.

Bioorganic & medicinal chemistry (2015-02-05)
Tsong-Long Hwang, Wen-Hui Wang, Ting-Yi Wang, Huang-Ping Yu, Pei-Wen Hsieh
ABSTRACT

Proteinase 3 (Pr3), and human neutrophil elastase (HNE) are two major neutrophilic serine proteases (NsPs) expressed in neutrophil azurophil granules. Emerging data suggest that excessive release of proteases mediates tissue damage, and therefore prolonged neutrophil accumulation has an important role in the pathogenesis of many diseases. Thus, HNE and Pr3 inhibitors may prove to be targets for the generation of agents in the treatment of neutrophilic inflammatory disease. Sivelestat is the only commercially available selective HNE inhibitor. Therefore, sivelestat was chosen as the model structure in an attempt to obtain more potent anti-NsPs agents. In the present study, a series 2-aminobenzaldehyde oxime and 2-aminobenzoate analogs were synthesized and their inhibitory effects on NsPs (CatG, Pr3, and HNE) were determined, respectively. The results of structure-activity relationships studies concluded that a hydroxyl oxime moiety plays an important role in ligand-enzyme affinity through hydrogen bonding. As compound 6 had more potency and showed dual inhibitory effects on NE and Pr3, both in vitro and in vivo experiments were carried out to evaluate its selectivity, effects in cell-based assays, and efficacy in models of inflammation and damage. Compound 6 had the potential to reduce paw edema induced by LPS and HNE, as well as acute lung injury, and may be approved as a candidate for the development of new agents in the treatment of neutrophilic inflammatory diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
o-Dianisidine dihydrochloride, Suitable for use in glucose determination
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrogen chloride solution, 3 M in cyclopentyl methyl ether (CPME)
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Chlorosulfonic acid, 99%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Trimethylacetyl chloride, 99%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 0.5 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 0.05 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 1 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium azide, SAJ first grade, ≥97.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 12 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid, JIS special grade, 35.0-37.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 0.2 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrogen chloride – ethanol solution, 0.1 M in ethanol
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 2 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 0.01 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid, SAJ first grade, 35.0-37.0%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 0.02 M
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Chlorosulfonic acid, CP
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 6 M
SKU
Pack Size
Availability
Price
Quantity
Supelco
Hydrogen chloride – 2-propanol solution, ~1.25 M HCl (T), for GC derivatization, LiChropur
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium azide, BioXtra
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium azide, ReagentPlus®, ≥99.5%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
N-Succinyl-Ala-Ala-Pro-Phe-7-amido-4-methylcoumarin, Leucine aminopeptidase substrate
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid, 36.5-38.0%, BioReagent, for molecular biology
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
o-Dianisidine dihydrochloride, ≥95%
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
o-Dianisidine dihydrochloride, tablet, 10 mg substrate per tablet
SKU
Pack Size
Availability
Price
Quantity
Supelco
Hydrochloric acid solution, volumetric, 0.1 M HCl (0.1N), endotoxin free
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Hydrochloric acid solution, 1.0 N, BioReagent, suitable for cell culture
SKU
Pack Size
Availability
Price
Quantity
Supelco
Hydrogen chloride – methanol solution, ~1.25 m HCl (T), for GC derivatization, LiChropur
SKU
Pack Size
Availability
Price
Quantity
Supelco
Hydrogen chloride – ethanol solution, ~1.25 M HCl, for GC derivatization, LiChropur
SKU
Pack Size
Availability
Price
Quantity
Sigma-Aldrich
Sodium azide, purum p.a., ≥99.0% (T)
SKU
Pack Size
Availability
Price
Quantity