Synthesis and SAR studies of bis-chromenone derivatives for anti-proliferative activity against human cancer cells

Article abstract of DOI:10.1016/j.bmcl.2014.09.057

A novel family of 3-((4-oxo-4H-chromen-3-yl)methyl)-4H-chromen-4-one (bis-chromone) derivatives were designed, synthesized and studied for their anti-cancer activity using the XTT assay for the growth inhibition against various human cancer cells. Among them, 3-((5-(cyclohexylmethoxy)-4-oxo-4H-chromen-3-yl)methyl)-7-methoxy-4H-chromen-4-one and 3-((5-(cyclohexylmethoxy)-4-oxo-4H-chromen-3-yl)methyl)-7-hydroxy-4H-chromen-4-one showed micromolar level of in vitro anti-proliferative activity against human cancer cell lines. The SAR studies indicated bis-chromone as a basic scaffold to design anticancer agents. The 5-cyclohexylmethoxy on the first chromenone ring and electron donating group such as CH₃, OCH₃ or hydrogen bonding group (OH) on the other chromenone ring of bis-chromone increased the activity. However, saturation of one of chromenone to chromanone in bis-chromones decreased the activity.