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

International Journal of Molecular Sciences

You-Ren Chen³  Chih-Hua Tseng¹  Yeh-Long Chen³  Tsong-Long Hwang²  Cherng-Chyi Tzeng³ 

[1] School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mail:;Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, and Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan;Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan; E-Mails:

关键词: benzo[f]indole-4;    9-dione derivatives;    superoxide anion generation;    elastase release;    anti-inflammatory agents;   

DOI  :  10.3390/ijms16036532

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.