Efficient synthesis and antiproliferative activity of novel thioether-substituted flavonoids

•A microwave-assisted synthesis of thioether-substituted flavonoids was developed.•57 novel flavonoids were synthesized and screened against six tumor cell lines.•Three candidates with promising antitumor activity were successfully identified.

As widely occurring natural products, flavonoids are an important source for drug discovery, due to their structural diversity and broad-spectrum biological activity. In this work, a library of novel, thioether-substituted flavonoids with diverse heterocyclic groups was synthesized via a microwave-assisted procedure with the advantages of good yields, short times, mild conditions and ready isolation of the products. Their antiproliferative activities were evaluated against six cancer cell lines, HCCLM-7, Hela, MDA-MB-435S, SW-480, Hep-2, and MCF-7 by the MTT-based assay. Compared with the positive control 5-fluorouracil, three compounds, 6a, 6b and 6j were successfully identified as the most promising candidates, due to their higher potency and broad-spectrum bioactivity with IC50 values in the range of 0.43 μM–6.7 μM.

Graphical abstractA library of 57 novel flavonoids bearing diverse heterocyclic groups was efficiently synthesized via microwave-assisted procedure. Three candidates with promising potent and broad-spectrum antitumor activity were successfully identified.Figure optionsDownload full-size imageDownload as PowerPoint slide