Discovery of benzo[f]indole-4,9-dione derivatives as new types of anti-inflammatory agents

You Ren Chen; Chih Hua Tseng; Yeh Long Chen; Tsong Long Hwang; Cherng Chyi Tzeng

doi:10.3390/ijms16036532

Discovery of benzo[f]indole-4,9-dione derivatives as new types of anti-inflammatory agents

You Ren Chen, Chih Hua Tseng, Yeh Long Chen, Tsong Long Hwang^*, Cherng Chyi Tzeng

^*Corresponding author for this work

School of Traditional Chinese Medicine

Research output: Contribution to journal › Journal Article › peer-review

15 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	6532-6544
Number of pages	13
Journal	International Journal of Molecular Sciences
Volume	16
Issue number	3
DOIs	https://doi.org/10.3390/ijms16036532
State	Published - 23 03 2015

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Publisher Copyright:
© 2015 by the authors; licensee MDPI, Basel, Switzerland.

Keywords

9-dione derivatives
Anti-inflammatory agents
Benzo[f]indole-4
Elastase release
Superoxide anion generation

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@article{d46163113ff8416cb4be32c1e91cf54a,

title = "Discovery of benzo[f]indole-4,9-dione derivatives as new types of anti-inflammatory agents",

abstract = "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.",

keywords = "9-dione derivatives, Anti-inflammatory agents, Benzo[f]indole-4, Elastase release, Superoxide anion generation",

author = "Chen, {You Ren} and Tseng, {Chih Hua} and Chen, {Yeh Long} and Hwang, {Tsong Long} and Tzeng, {Cherng Chyi}",

note = "Publisher Copyright: {\textcopyright} 2015 by the authors; licensee MDPI, Basel, Switzerland.",

year = "2015",

month = mar,

day = "23",

doi = "10.3390/ijms16036532",

language = "英语",

volume = "16",

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T1 - Discovery of benzo[f]indole-4,9-dione derivatives as new types of anti-inflammatory agents

AU - Chen, You Ren

AU - Tseng, Chih Hua

AU - Chen, Yeh Long

AU - Hwang, Tsong Long

AU - Tzeng, Cherng Chyi

PY - 2015/3/23

Y1 - 2015/3/23

N2 - 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.

AB - 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.

KW - 9-dione derivatives

KW - Anti-inflammatory agents

KW - Benzo[f]indole-4

KW - Elastase release

KW - Superoxide anion generation

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U2 - 10.3390/ijms16036532

DO - 10.3390/ijms16036532

M3 - 文章

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AN - SCOPUS:84925856825

SN - 1661-6596

VL - 16

SP - 6532

EP - 6544

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 3

ER -

Discovery of benzo[f]indole-4,9-dione derivatives as new types of anti-inflammatory agents

Abstract

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Keywords

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