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.

Graphical abstractA 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 full-size imageDownload as PowerPoint slide