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 IC50 value of 5.0 mu M against beta- glucuronidase release, was more potent than its tricyclic furo[2,3-b]quinoline isomer 3a (> 30 mu M), its 4'-COMe counterpart 7 (7.5 mu M), and its oxime derivative 13a (11.4 mu M) and methyloxime derivative 13b (> 30 mu M). For the inhibition of lysozyme release, however, oxime derivative 12a (8.9 mu M) and methyloxime derivative 12b (10.4 mu M) 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 IC50 value of 4.6 mu M, while 8 is the most active against beta-glucuronidase release with an IC50 value of 5.0 mu M. (E)-1-{3-[(2-Furan-2-yl)quinolin-4-yloxy]phenyl}ethanone oxime (11a) is capable of inhibiting both lysozyme and P-glucuronidase release with IC50 values of 7.1 and 9.5 mu M, 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 IC50 value of 2.3 mu M which is more potent than genistein (9.1 mu M). For the inhibitory activity of fMLP-induced superoxide anion generation, 11a (2.7 mu M), 11b (2.8 mu M), and 13b (2.2 mu M) are three of the most active. None of above compounds exhibited significant cytotoxicity. (c) 2006 Elsevier Ltd. All rights reserved.