Synthesis, antiproliferative and anti-dengue virus evaluations of 2-aroyl-3-arylquinoline derivatives

• A series of 2-aroyl-3-arylquinoline derivatives were synthesized.
• 13a and 17 inhibit the DENV2 RNA expression with potency approximately equal to that of ribavirin.
• Compounds 19a–19c showed potent cytotoxicity as that of topotecan.

A number of 2-aroyl-3-arylquinoline derivatives was synthesized and evaluated for their anti-Dengue virus activity. Both 2-(hydroxyphenylmethyl)-3-(4-methoxyphenyl)quinoline (13a) and 2-(4-hydroxybenzoyl)-3-(4-hydroxyphenyl)quinoline (17) were found to significantly inhibit the DENV2 RNA expression in Huh-7-DV-Fluc cells with a potency approximately equal to that of ribavirin and the inhibition is in a dose-dependent manner. Compounds 13a and 17 reduced DENV replication in both viral protein and mRNA levels, and no significant cell cytotoxicity was detected, with greater than 50% viability of Huh-7-DV-Fluc cells at a concentration of 100 μM. However, significant cytotoxicity was detected for the positive ribavirin. In addition, we performed infectious assay to further verify the inhibitory activity of 13a and 17 on DENV replication in protein and RNA levels. On the other hand, compounds 19a–19c exhibited IC50 values ranged from 4.47 to 8.68 μM against A549, H1299, MCF-7, and Huh-7 which were approximately equal potent to the positive topotecan. Structural optimization of lead compounds, 13a and 17, and their detailed molecular mechanism of action are ongoing.

A number of 2-aroyl-3-arylquinoline derivatives were synthesized and evaluated for their anti-Dengue virus activity. Both 13a and 17 were found to significantly inhibit the DENV2 RNA expression in Huh-7-DV-Fluc cells.Figure optionsDownload as PowerPoint slide