1. Carbazole alkaloids with antiangiogenic activities from Clausena sanki.
- Author
-
Wei R, Ma Q, Li T, Liu W, Sang Z, Li M, and Liu S
- Subjects
- Alkaloids chemistry, Alkaloids isolation & purification, Angiogenesis Inhibitors chemistry, Angiogenesis Inhibitors isolation & purification, Animals, Carbazoles chemistry, Carbazoles isolation & purification, Cell Proliferation drug effects, Dose-Response Relationship, Drug, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Molecular Structure, Structure-Activity Relationship, Vascular Endothelial Growth Factors metabolism, Zebrafish embryology, Alkaloids pharmacology, Angiogenesis Inhibitors pharmacology, Carbazoles pharmacology, Clausena chemistry, Vascular Endothelial Growth Factors antagonists & inhibitors
- Abstract
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 IC
50 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., (Copyright © 2018 Elsevier Inc. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF