title: Synthesis and biological evaluation of N-(4-hydroxy-3-mercaptonaphthalen-1-yl)amides as inhibitors of angiogenesis and tumor growth.
abstract: A series of N-(4-hydroxy-3-mercaptonaphthalen-1-yl)amides were synthesized and investigated for their in vitro antiangiogenic activity. Among these compounds, 6d, which possesses an ortho-nitro group at the benzene ring, exhibited potent inhibitory effect on the proliferation of HUVECs, A549, K562, PC-3, HCT116, MDA-MB-231 and MCF-7 cells (IC50 = 5.34, 40.53, 10.81, 52.52, 10.19, 21.37 and 2.81 μM, respectively). Meanwhile, compound 6d inhibited in vitro angiogenesis markedly in both HUVECs tube formation assay and the rat thoracic aorta rings test. Further kinase assay study showed that compound 6d had good VEGFR2, ALK, AKT1 and ABL inhibitory activities and moderate EGFR and PDGFR-β inhibitory activities. The data supports the further investigation of this class of compounds as potential antiangiogenic and anticancer agents.
authors: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors: Fuming
authors: F
authors: Xu
authors: Yuping
authors: Y
authors: Jia
authors: Qingli
authors: Q
authors: Wen
authors: Xuejian
authors: X
authors: Wang
authors: Lei
authors: L
authors: Zhang
authors: Yingjie
authors: Y
authors: Zhang
authors: Kanghui
authors: K
authors: Yang
authors: Wenfang
authors: W
authors: Xu
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001013:Aorta, Thoracic / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents