Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors

Yanzhao Xu; Na Qi; Hui Wen; Gang Zhang; Yuchen Wang; Huaqing Cui

doi:10.1007/s00044-020-02684-4

Synthesis and evaluation of benzenesulfonic acid derivatives as human neutrophil elastase (hNE) inhibitors

Med Chem Res. 2021;30(2):387-398. doi: 10.1007/s00044-020-02684-4. Epub 2021 Jan 12.

Authors

Yanzhao Xu¹, Na Qi¹, Hui Wen¹, Gang Zhang¹, Yuchen Wang¹, Huaqing Cui¹

Affiliation

¹ State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xiannongtan Street, Beijing, 100050 China.

Abstract

Herein we report our investigation concerning the development of Human neutrophil elastase (hNE) inhibitors for the treatment of Acute Respiratory Distress Syndrome (ARDS). Various benzenesulfonic acid derived compounds were synthesized and evaluated as competitive inhibitors of hNE. Biological screening revealed that compound 4f shows moderate inhibitory activity (IC₅₀ = 35.2 μM) against hNE. Compound 4f was also superimposed onto the active center of hNE to understand the binding mode.

Keywords: ARDS; Benzenesulfonic acid; Drug design; Human neutrophil elastase; Inhibitor.