Synthesis and biological evaluation of nigranoic acid esters as novel human neutrophil elastase inhibitors

Abstract

Human neutrophil elastase (HNE) has been implicated as a major contributor in the pathogenesis of diseases, such as lung disorders and other inflammatory diseases. A series of 12 new nigranoic acid esters were regioselectively synthesised in good yields and evaluated for HNE inhibitory activity. Nigranoic acid exhibited significant inhibitory activity against HNE with the IC₅₀ value of 3.77 μM, and six esters displayed considerable inhibitory effects on HNE with IC₅₀ values in the range of 2.61–8.95 μM. The nigranoic acid esters having phenyls substituted with bromine and trimethoxyls (3h and 3b) showed stronger inhibitory activity on HNE than nigranoic acid.

Keywords::

• nigranoic acid esters
• human neutrophil elastase
• inhibition

Funding

This work was financially supported by the Yunnan Province of China [grant number 2009CC018] for basic research in social development and the applied basic research projects of Yunnan Province [grant number 2014FZ042].

Notes

^1. Guoli Huang and Li Feng contributed equally to this work.