Synthesis, cytotoxicity, and anti-inflammatory evaluation of 2-(furan-2-yl)-4-(phenoxy)quinoline derivatives. Part 4.
A number of 2-(furan-2-yl)-4-phenoxyquinoline derivatives have been synthesized and evaluated for anti-inflammatory evaluation. 4-[(2-Furan-2-yl)quinolin-4-yloxy]benzaldehyde (8), with an IC(50) value of 5.0 microM against beta-glucuronidase release, was more potent than its tricyclic furo[2,3-b]quinoline isomer 3a (>30 microM), its 4'-COMe counterpart 7 (7.5 microM), and its oxime derivative 13a (11.4 microM) and methyloxime derivative 13b (>30 microM). For the inhibition of lysozyme release, however, oxime derivative 12a (8.9 microM) and methyloxime derivative 12b (10.4 microM) are more potent than their ketone precursor 7 and their respective tricyclic furo[2,3-b]quinoline counterparts 4a and 4b. Among them, 4-[4-[(2-furan-2-yl)-quinolin-4-yloxy]phenyl]but-3-en-2-one (10) is the most active against lysozyme release with an IC(50) value of 4.6 microM, while 8 is the most active against beta-glucuronidase release with an IC(50) value of 5.0 microM. (E)-1-[3-[(2-Furan-2-yl)quinolin-4-yloxy]phenyl] ethanone oxime (11a) is capable of inhibiting both lysozyme and beta-glucuronidase release with IC(50) values of 7.1 and 9.5 microM, respectively. For the inhibition of TNF-alpha formation, 1-[3-[(2-furan-2-yl)quinolin-4-yloxy]phenyl]ethanone (6) is the most potent with an IC(50) value of 2.3 microM which is more potent than genistein (9.1 microM). For the inhibitory activity of fMLP-induced superoxide anion generation, 11a (2.7 microM), 11b (2.8 microM), and 13b (2.2 microM) are three of the most active. None of above compounds exhibited significant cytotoxicity.
Chen
Yeh-Long
YL
Faculty of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Zhao
Yue-Ling
YL
Lu
Chih-Ming
CM
Tzeng
Cherng-Chyi
CC
Wang
Jih-Pyang
JP
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D015550:Cell Degranulation; D002478:Cells, Cultured; D064420:Drug-Related Side Effects and Adverse Reactions; D005663:Furans / Q000737:chemistry*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C512499:2-(furan-2-yl)-4-(phenoxy)quinoline; D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha