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.
authors: Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. u98850003@cc.kmu.edu.tw.
authors: You-Ren
authors: YR
authors: Chen
authors: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan. chihhua@kmu.edu.tw.
authors: Chih-Hua
authors: CH
authors: Tseng
authors: Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. yeloch@kmu.edu.tw.
authors: Yeh-Long
authors: YL
authors: Chen
authors: 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. htl@mail.cgu.edu.tw.|Immunology Consortium, Chang Gung Memorial Hospital, Kweishan, Taoyuan 333, Taiwan. htl@mail.cgu.edu.tw.
authors: Tsong-Long
authors: TL
authors: Hwang
authors: Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan. tzengch@kmu.edu.tw.
authors: Cherng-Chyi
authors: CC
authors: Tzeng
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000893:Anti-Inflammatory Agents; D019272:Leukocyte Elastase