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Design and semisynthesis of oleanolic acid derivatives as VEGF in- hibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs

文献类型：期刊论文

作者Meng Ning2; Xie Hong-Xu2; Hou Jia-Rong2; Chen Yon-Bin2; Wu Meng-Jun1; Guo Yue-Wei1; Jiang Cheng-Shi2
刊名CHINESE JOURNAL OF NATURAL MEDICINES
出版日期2022-03-01
卷号20期号:3页码:229-240
关键词Oleanolic acid Structural modification VEGF inhibitor VEGFR2 Angiogenesis
ISSN号2095-6975
DOI10.1016/S1875-5364(22)60159-6
通讯作者Meng Ning(mls_mengn@ujn.edu.cn) ; Guo Yue-Wei(ywguo@simm.ac.cn) ; Jiang Cheng-Shi(bio_jiangcs@ujn.edu.cn)
英文摘要Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing alpha,beta-unsat-urated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGFinduced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.
WOS关键词ENDOTHELIAL GROWTH-FACTOR ; CANCER
资助项目National Natural Science Foundation of China[21672082] ; National Natural Science Foundation of China[31671214] ; Natural Science Foundation of Shandong Province[ZR2019YQ31] ; Natural Science Foundation of Shandong Province[ZR2020YQ52] ; Natural Science Foundation of Shandong Province[ZR2020MB103] ; Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program[2020KJE006] ; Science and Technology Project of University of Jinan[XKY2004]
WOS研究方向Integrative & Complementary Medicine ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000783832900009
出版者CHINESE JOURNAL NATURAL MEDICINES
源URL[http://119.78.100.183/handle/2S10ELR8/299770]  
专题新药研究国家重点实验室
通讯作者Meng Ning; Guo Yue-Wei; Jiang Cheng-Shi
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Peoples R China
推荐引用方式
GB/T 7714		 Meng Ning,Xie Hong-Xu,Hou Jia-Rong,et al. Design and semisynthesis of oleanolic acid derivatives as VEGF in- hibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs[J]. CHINESE JOURNAL OF NATURAL MEDICINES,2022,20(3):229-240.
APA Meng Ning.,Xie Hong-Xu.,Hou Jia-Rong.,Chen Yon-Bin.,Wu Meng-Jun.,...&Jiang Cheng-Shi.(2022).Design and semisynthesis of oleanolic acid derivatives as VEGF in- hibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs.CHINESE JOURNAL OF NATURAL MEDICINES,20(3),229-240.
MLA Meng Ning,et al."Design and semisynthesis of oleanolic acid derivatives as VEGF in- hibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs".CHINESE JOURNAL OF NATURAL MEDICINES 20.3(2022):229-240.

入库方式： OAI收割

来源：上海药物研究所

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