Synthesis and biological evaluation of hydroxylated 3-phenylcoumarins as antioxidants and antiproliferative agents

Based on the observed biological activities of coumarins and resveratrol, we synthesized fourteen hydroxylated 3-phenylcoumarins (stilbene-coumarin hybrids) including six novel ortho-hydroxy-methoxy substituted derivatives, 1–14, by Perkin reaction. We characterized these compounds concerning their antioxidant activity against 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH)-induced pBR322 DNA strand breakage, and their antiproliferative effects on human promyelocytic leukemia HL-60 and human lung adenocarcinoma epithelial A549 cells. Structure–activity relationship information suggests that the introduction of ortho-hydroxy-methoxy groups and ortho-dihydroxy groups on the aromatic A ring could efficiently improve antiproliferative activity. Interestingly, a new derivative, 6-methoxy-7-hydroxy-3-(4′-hydroxyphenyl)coumarin, 9, behaved as a poor antioxidant but appeared to be the most potent antiproliferative agent among the compounds examined, and this activity was mediated by deregulation in cell cycle and induction of apoptosis.

A new stilbene-coumarin hybrid, 6-methoxy-7-hydroxy-3-(4′-hydroxyphenyl)coumarin, 9, behaved as a poor antioxidant but appeared to be the most potent antiproliferative agent among the synthesized 3-phenylcoumarins, and this activity was mediated by deregulation in cell cycle and induction of apoptosis.Figure optionsDownload as PowerPoint slide