Synthesis, cytotoxicity, and anti-inflammatory evaluation of 2-(furan-2-yl)-4-(phenoxy)quinoline derivatives. Part 4 Original Research Article

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 μM against β-glucuronidase release, was more potent than its tricyclic furo[2,3-b]quinoline isomer 3a (>30 μM), its 4′-COMe counterpart 7 (7.5 μM), and its oxime derivative 13a (11.4 μM) and methyloxime derivative 13b (>30 μM). For the inhibition of lysozyme release, however, oxime derivative 12a (8.9 μM) and methyloxime derivative 12b (10.4 μM) 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 μM, while 8 is the most active against β-glucuronidase release with an IC50 value of 5.0 μM. (E)-1-{3-[(2-Furan-2-yl)quinolin-4-yloxy]phenyl}ethanone oxime (11a) is capable of inhibiting both lysozyme and β-glucuronidase release with IC50 values of 7.1 and 9.5 μM, respectively. For the inhibition of TNF-α formation, 1-{3-[(2-furan-2-yl)quinolin-4-yloxy]phenyl}ethanone (6) is the most potent with an IC50 value of 2.3 μM which is more potent than genistein (9.1 μM). For the inhibitory activity of fMLP-induced superoxide anion generation, 11a (2.7 μM), 11b (2.8 μM), and 13b (2.2 μM) are three of the most active. None of above compounds exhibited significant cytotoxicity.