Synthesis and in vitro anticancer activity of 6,7-methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-one analogs

6,7-Methylenedioxy (or 5-hydroxy-6-methoxy)-2-(substituted selenophenyl)quinolin-4-ones and their isosteric compounds were synthesized and evaluated for anticancer activity. Structure–activity relationships (SAR) of these compounds were established. Among all tested compounds, 6,7-methylenedioxy-2-(5-methylselenophen-2-yl)quinolin-4-one (4d) was found to be the most promising anticancer agent. In screening against NCI’s 60 human tumor cell line panel, 4d exhibited highly selective and potent inhibitory activity against MDA-MB-435 melanoma. Furthermore, the results of COMPARE analysis suggested that 4d is an antimitotic agent with a different mechanism of action from the conventional antimitotic agents, such as colchicine, vinca alkaloids and paclitaxel. Therefore, 4d was identified as a new lead compound that merits further optimization.

The following 2-selenophenyl quinolones (4d, 4k, 7a and 7e) and their analogs were synthesized. Their in vitro antiproliferative activities against human cancer cell lines were evaluated .Figure optionsDownload as PowerPoint slideHighlights
► A series of 2-selenophenyl quinolones were synthesized.
► Compound 4d exhibited selective and potent activity against MDA-MB-435 cells.
► The action mechanism of 4d differs from colchicine, vinblastine and Paclitaxel.
► The SAR of 4a–f is selenophenyl derivatives ≥thienyl derivatives >furyl derivatives.
► The SAR of 4g–l is 5-OH-6-OCH3 derivatives >6-OCH3 derivatives >5,6-OCH3 derivatives.