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Carbazole alkaloids with antiangiogenic activities from Clausena sanki
Affiliation:1. Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;2. College of Pharmacy, Jiangxi Science & Technology Normal University, Nanchang 330013, China;3. College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China;4. The Health Team Armed Police Detachment from Kaifeng City, Kaifeng 475000, China;1. Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Molecular Science, Shanxi University, Taiyuan 030006, PR China;2. Key Laboratory of Materials and Computational Chemistry, Department of Chemistry, Xinzhou Teachers University, Xinzhou 034000, PR China;1. College of Agriculture, Jiangxi Agricultural University, Nanchang 330045, China;2. Jiangxi Key Laboratory of Natural Products and Functional Food, Jiangxi Agricultural University, Nanchang 330045, China;3. Jiangxi Yichun University, Yichun 336000, China;1. Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, UPM, 43400, Selangor Darul Ehsan, Malaysia;2. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA;3. Division of Pharmacognosy, Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, University, MS, 38677, USA;4. Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, UPM, 43400, Selangor Darul Ehsan, Malaysia;5. Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM, 43400, Selangor Darul Ehsan, Malaysia;1. Department of Chemistry, Bharathiar University, Coimbatore, 641 046, India;2. Translational Research Lab, Department of Biotechnology, Bharathiar University, Coimbatore, 641 046, India;3. Department of Chemistry, University of North Texas, 1155 Union Circle, #305070, Denton, TX, 76203, United States;1. Organic Materials Laboratory, Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247667, India;2. Department of Materials Science and Engineering, National Tsing-Hua University, Hsinchu, 30013, Taiwan, ROC
Abstract:Two new carbazole alkaloids 1 and 2, and eleven known congeners 313 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 113 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 113 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.
Keywords:Rutaceae  Carbazole alkaloid  Antiangiogenic activity
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