Design, synthesis and discovery of 5-hydroxyaurone derivatives as growth inhibitors against HUVEC and some cancer cell lines

• Published in: European journal of medicinal chemistry Vol. 45; no. 12; pp. 5950 - 5957
• Main Authors: Cheng, Huimin, Zhang, Lianwen, Liu, Yingxue, Chen, Shaopeng, Cheng, Hao, Lu, Xin, Zheng, Zhuxia, Zhou, Guo-Chun
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.12.2010; Elsevier
• Subjects: 5-Hydroxyaurone; Anti-angiogenesis agent; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Benzofurans - chemical synthesis; Benzofurans - chemistry; Benzofurans - pharmacology; Benzylidene Compounds - chemical synthesis; Benzylidene Compounds - chemistry; Benzylidene Compounds - pharmacology; Biological and medical sciences; Cell invasion; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Chemistry, Medicinal; Conventional anticancer agent; Drug Discovery; Drug Screening Assays, Antitumor; Endothelial Cells - drug effects; General aspects; Humans; Life Sciences & Biomedicine; Medical sciences; Molecular Structure; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Stereoisomerism; Structure-Activity Relationship; Tube formation; Tube formation; Anti-angiogenesis agent; Cell invasion; 5-Hydroxyaurone; Conventional anticancer agent; Cell migration; AURONES; ANGIOGENESIS; ANALOGS; RESISTANCE; FLAVONES; Antineoplastic agent; Endothelial cell; Lung; Cytotoxicity; Oxygen heterocycle; Flavonoid; Structure activity relation; Blood vessel; Bicyclic compound; Mammary gland; Antiangiogenic agent; Chemical synthesis; Tumor cell; Human; Benzene derivatives; Antimetastatic agent; Aniline derivatives; In vitro; Ketophenols; Cell line; Umbilical vein; Aromatic amine
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.09.061

A series of 4′-substituted 5-hydroxyaurone derivatives were synthesized and their inhibitory activities against the proliferation of endothelial cells and two cancer cell lines were studied. Some of these compounds functioned as potent inhibitors against the proliferation of endothelial cells and cancer cells but possessed much weaker cytotoxic activities against non-cancer cell line of CCC-HPF-1. It was demonstrated that two most active compounds 16 and 27 effectively inhibited in vitro endothelial cell motility and tube formation, which are basic properties of endothelial cells for angiogenesis. Moreover, 16 and 27 also showed significant activities against in vitro cancer cell invasion, indicating that they have potential to inhibit cancer metastasis. These composite results suggest that 4′-substituted 5-hydroxyaurone is indeed a candidate structural scaffold for anticancer agent targeting activated endothelial cells and fast-proliferating cancer cells. 5-Hydroxyaurone compounds 16 and 27 exhibited potent inhibitory activity against the proliferation of endothelial cells and cancer cells. They effectively inhibited in vitro endothelial cell motility and tube formation and also in vitro cancer cell invasion. [Display omitted] ►4′-Substituted 5-hydroxyaurone derivatives were synthesized and their inhibitory activities were studied. ►Some compounds functioned as potent inhibitors against the proliferation of endothelial cells and cancer cells. ►Two most active compounds effectively inhibited in vitro endothelial cell motility and tube formation and in vitro cancer cell invasion.