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Human neutrophil elastase inhibitory dihydrobenzoxanthones and alkylated flavones from the Artocarpus elasticus root barks

Authors
  • Ban, Yeong Jun1
  • Baiseitova, Aizhamal1
  • Nafiah, Mohd Azlan2
  • Kim, Jeong Yoon1
  • Park, Ki Hun1
  • 1 Gyeongsang National University, Jinju, 52828, Republic of Korea , Jinju (South Korea)
  • 2 Universiti Pendidikan Sultan Idris, Tg. Malim, Perak, 35900, Malaysia , Tg. Malim (Malaysia)
Type
Published Article
Journal
Applied Biological Chemistry
Publisher
Springer Singapore
Publication Date
Sep 29, 2020
Volume
63
Issue
1
Identifiers
DOI: 10.1186/s13765-020-00549-3
Source
Springer Nature
Keywords
License
Green

Abstract

Neutrophil elastases are deposited in azurophilic granules interspace of neutrophils and tightly associated with inflammatory ailments. The root barks of Artocarpus elasticus had a strong inhibitory potential against human neutrophil elastase (HNE). The responsible components for HNE inhibition were confirmed as alkylated flavones (2–4, IC50 = 14.8 ~ 18.1 μM) and dihydrobenzoxanthones (5–8, IC50 = 9.8 ~ 28.7 μM). Alkyl groups on flavone were found to be crucial functionalities for HNE inhibition. For instance, alkylated flavone 2 (IC50 = 14.8 μM) was 20-fold potent than mother compound norartocarpetin (1, IC50 > 300 μM). The kinetic analysis showed that alkylated flavones (2–4) were noncompetitive inhibition, while dihydrobenzoxanthones (5–8) were a mixed type I (KI < KIS) inhibitors, which usually binds with free enzyme better than to complex of enzyme–substrate. Inhibitors and HNE enzyme binding affinities were examined by fluorescence quenching effect. In the result, the binding affinity constants (KSV) had a significant correlation with inhibitory potencies (IC50).

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