Recent advances in the development of elastase inhibitors

• Published in: Future medicinal chemistry 2020-10, Vol.12 (20), p.1809-1813
• Main Authors: Donarska, Beata, Z Łączkowski, Krzysztof
• Format: Article
• Language: English
• Subjects: Arteriosclerosis; Boron; cancer; Chronic obstructive pulmonary disease; COPD; Elastase; Emphysema; Enzymes; Esters; Heparan sulfate; human neutrophil elastase; Hydrogen bonding; Hydrogen bonds; Indoles; inflammatory diseases; Lung diseases; Neutrophils; Nitrogen; Obstructive lung disease; Physiology; Rheumatoid arthritis; Ursolic acid
• ISSN: 1756-8919; 1756-8927
• DOI: 10.4155/fmc-2020-0163

Due to the fact that a large amount of elastase is released during inflammation, it is involved in the pathogenesis of diseases such as emphysema, chronic obstructive pulmonary disease, acute respiratory failure, atherosclerosis, rheumatoid arthritis or cancer (1). Hasdemir et al. synthesized aryl and heteroaryl γ-hydroxy-, γ-methoxyimino-and γ-benzyloxyiminobutyric acid methyl esters and showed that only compounds containing phenyl and p-chlorophenyl group possessed higher activity against elastase than the standard ursolic acid (3). [...]the authors stated that the impact of the effects of distortion energy of docked molecules on the formation of the Michaelis complex may be the main factor determining the activity of compounds. The indazole system forms a hydrogen bond with Ser195 or Gly193, and the indole system due to the lack of a nitrogen atom in position 2 cannot form hydrogen bonds with HNE, which may be responsible for drastically different inhibitory activity.