Synthesis and cytotoxic activity of novel chromenes

With the aim of discovering potential cytotoxic agents, a new series of substituted 4-chromenes were synthesized in three steps starting from the readily available 4-chromanone 3. Alkylation of compound 3 afforded alkyne 4-chromanone 5, which on subsequent cyclization provided pyranochromene 10. Reaction of compounds 5 and 10 with Grignard reagents yielded the desired compounds 7, 8a-d/9a-9d, 12a-b and 14a-c/15a-c. The synthesized compounds were evaluated for their cytotoxic activity on three different cell lines, namely HT29, T47D and L929 and most of them were shown to be relatively good with IC50= 100-130 mu M. Among them, 14b/15b and 8c/9c were the most potent ones with the IC50= 92.28 +/- 16.84 (on HT29) and 94.48 +/- 15.37 mu M (on T47D), respectively.