title: Synthesis and biological evaluation of hydroxylated 3-phenylcoumarins as antioxidants and antiproliferative agents.
abstract: 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.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Guo-Yun
authors.initials: GY
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Dai
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Cao
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Kang
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Hu
authors.forename: Jiang-Jiang
authors.initials: JJ
authors.lastname: Tang
authors.forename: Xiu-Zhuang
authors.initials: XZ
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Jin
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D003374:Coumarins