title: Structural modification of honokiol, a biphenyl occurring in Magnolia officinalis: the evaluation of honokiol analogues as inhibitors of angiogenesis and for their cytotoxicity and structure-activity relationship.
abstract: Honokiol, widely known as an antitumor agent, has been used as an antiangiogenesis drug lead. In this paper, 47 honokiol analogues and derivatives were investigated for their antiangiogenic activity by application of the transgenic zebrafish screening model, antiproliferative and cytotoxic activity against HUVECs, and three tumor cell lines by MTT assay. 3',5-Diallyl-2,4'-dihydroxy-[1,1'-biphen-yl]-3,5'-dicarbaldehyde (8c) was found to suppress the newly grown segmental vessels from the dorsal aorta of zebrafish and prevent inappropriate vascularization as well as exhibit more potent inhibitory effects on the proliferation of HUVECs, A549, HepG2, and LL/2 cells (IC(50) = 15.1, 30.2, 10.7, and 21.7 μM, respectively) than honokiol (IC(50) = 52.6, 35.0, 16.5, and 65.4 μM, respectively). Analogue 8c also effectively inhibited the migration and capillary-like tube formation of HUVECs in vitro. The antiangiogenic effect and antiproliferative activity of these structurally modified honokiol analogues and derivatives have led to the establishment of a structure-activity relationship.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.forename: Jinying
authors.initials: J
authors.lastname: Chen
authors.forename: Xuewei
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Youfu
authors.initials: Y
authors.lastname: Luo
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Tianen
authors.initials: T
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Peng
authors.forename: Shucai
authors.initials: S
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Jie
authors.forename: Aihua
authors.initials: A
authors.lastname: Peng
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001547:Benzaldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004625:Embryo, Nonmammalian / Q000098:blood supply; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D031566:Magnolia; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013329:Structure-Activity Relationship; D015027:Zebrafish; D010636:Phenols
chemical_list: D000498:Allyl Compounds; D020533:Angiogenesis Inhibitors; D001547:Benzaldehydes; D001713:Biphenyl Compounds; D017705:Lignans; C568506:3',5-diallyl-2,4'-dihydroxy-(1,1'-biphenyl)-3,5'-dicarbaldehyde; C005499:honokiol; D010636:Phenols