Discovery of Benzo[f]indole-4,9-dione Derivatives as New Types of Anti-Inflammatory Agents

Discovery of Benzo[f]indole-4,9-dione Derivatives as New Types of Anti-Inflammatory Agents

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Certain benzo[f]indole-4,9-dione derivatives were synthesized and evaluated for their inhibitory effects on superoxide anion generation and neutrophil elastase (NE) release in formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils. Results indicated that (Z)-1-benzyl-4-(hydr...

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Bibliographic Details
Main Authors: You-Ren Chen, Chih-Hua Tseng, Yeh-Long Chen, Tsong-Long Hwang, Cherng-Chyi Tzeng
Format: Article
Language:English
Published: MDPI AG 2015-03-01
Series:International Journal of Molecular Sciences
Subjects:
benzo[f]indole-4,9-dione derivatives
superoxide anion generation
elastase release
anti-inflammatory agents
Online Access:http://www.mdpi.com/1422-0067/16/3/6532
Description
Summary:Certain benzo[f]indole-4,9-dione derivatives were synthesized and evaluated for their inhibitory effects on superoxide anion generation and neutrophil elastase (NE) release in formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils. Results indicated that (Z)-1-benzyl-4-(hydroxyimino)-1H-benzo[f]indol-9(4H)-one (10) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 value of 2.78 and 2.74 μM respectively. The action mechanisms of 10 in human neutrophils were further investigated. Our results showed that compound 10 did not alter fMLF-induced phosphorylation of Src (Src family Y416). Notably, phosphorylation of Akt (S473) and mobilization of [Ca2+]i caused by fMLF was inhibited by compound 10. Further structural optimization of 10 is ongoing.
ISSN:1422-0067

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