Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2018-01-31 , DOI: 10.1016/j.bioorg.2018.01.032 Rongrui Wei , Qinge Ma , Tao Li , Wenmin Liu , Zhipei Sang , Mingbo Li , Saimei Liu
Two new carbazole alkaloids 1 and 2, and eleven known congeners 3–13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1–13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1, 2, 6, 8, and 13 (μM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC50 values of 12.1 (C.I. 8.2–15.2), 58.1 (C.I. 56.3–63.4), 13.7 (C.I. 9.2–15.4), 16.0 (C.I. 9.5–16.4), and 63.2 (C.I. 57.8–65.7) μM, respectively. Moreover, the antiangiogenic activities of compounds 1–13 were evidenced in vivo in the zebrafish embryo model. As a result, compounds 1, 2, 6, 8, and 13 showed effectively suppress angiogenesis. These research results may guide the search for new natural products with antiangiogenic attributes.
中文翻译:
具有抗血管生成活性的咔唑生物碱起Clausena sanki
两个新的咔唑生物碱1和2,和11个已知的同系物3 - 13分离并从识别的黄皮SANKI首次。根据广泛的UV,IR,MS,NMR光谱数据并与文献进行比较,阐明了它们的结构。化合物1 - 13用MTT法评价,以确定它们是否降低VEGF介导的细胞增殖的内皮细胞与阿昔替尼作为阳性对照。其中,化合物1,2,6,8,和13(μM)表现出中等的抗血管生成活性,在体外抑制VEGF诱导的HUVEC增殖,IC 50值分别为12.1(CI 8.2-15.2),58.1(CI 56.3-63.4),13.7(CI 9.2-15.4),16.0(CI 9.5) –16.4)和63.2(CI 57.8–65.7)μM。此外,化合物的抗血管生成活性1 - 13被证明在体内在斑马鱼胚胎模型。其结果,化合物1,2,6,8,和13显示出有效地抑制血管生成。这些研究结果可能指导寻找具有抗血管生成特性的新天然产物。