title: Design and synthesis of novel xyloketal derivatives and their vasorelaxing activities in rat thoracic aorta and angiogenic activities in zebrafish angiogenesis screen.
abstract: A novel series of xyloketal derivatives (1-21) were designed and prepared. The majority of the compounds demonstrated vasorelaxation action on 60 mM KCl-induced contractions rat isolated aortic rings in a concentration-dependent manner, and the action is mediated by both endothelium-independent and endothelium-dependent mechanisms. Compounds 9, 12, 13, 14, 15, and 19 showed higher vasorelaxation activities comparing with the lead compound 3. In addition, these derivatives had potential protective action against oxLDL-induced endothelial oxidative injury and enhanced NO production in HUVECs without toxic effects. The NO release was completely inhibited by eNOS inhibitor L-NAME. Furthermore, 3 significantly promoted the angiogenesis in zebrafish in a concentration-dependent manner at 0.1, 1, and 10 muM. Compounds 9, 12, 14, 16, 20, and 21 exhibited stronger angiogenic activities than 3. Therefore, xyloketal derivatives are unique compounds with multiple pharmacological properties and may have potential implications in the treatment of cardiovascular diseases.
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Xu
authors.forename: Yiying
authors.initials: Y
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.forename: Xilin
authors.initials: X
authors.lastname: Liu
authors.forename: Bingtai
authors.initials: B
authors.lastname: Lu
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Guanlei
authors.initials: G
authors.lastname: Wang
authors.forename: Jiyan
authors.initials: J
authors.lastname: Pang
authors.forename: Yongcheng
authors.initials: Y
authors.lastname: Lin
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D043925:Angiogenesis Inducing Agents; D008077:Lipoproteins, LDL; D011714:Pyrans; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; C438053:xyloketal A; C515343:xyloketal B; D009569:Nitric Oxide