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Differential: In vitro and in vivo anti-angiogenic activities of acetal and ketal andrographolide derivatives in HUVEC and zebrafish models
Dekuan Sheng2; Jingjing Li1; Kun Wang2; Yuran Peng2; Shang Li1; Yicheng Sun2; Zhuyun Liu2; Decai Wang2; Simon Ming Yuen Lee1; Guo-Chun Zhou2
2016
Source PublicationRSC Advances
ISSN20462069
Volume6Issue:105Pages:102831-102842
Abstract

A series of acetal and ketal derivatives of andrographolide were synthesized and their anti-angiogenic activities were tested in vitro and in vivo using HUVEC and zebrafish models, respectively. These compounds exhibited better angiogenesis inhibitory activity in both models than the parent compound andrographolide (1). The compounds' SARs differed for the HUVEC and zebrafish models, in that 14α-ketal 2 showed the best activity for in vivo anti-angiogenesis in zebrafish while 14α-acetals 4, 5 and 6 had greater in vitro anti-angiogenic activity with HUVECs than the other compounds and 1. The results suggested that methylene acetals 4, 5 and 6 were possibly hydrolyzed into 3 or 1 in zebrafish and that 14α-ketal 2 probably did not fully act as a pro-drug of 3 or 1 in zebrafish, instead exerting the anti-angiogenic effect itself or being metabolized into an unknown more active form(s) than 3 and 1 to block in vivo angiogenesis in zebrafish. The underlying molecular mechanisms of compound 2's action were explored and the results indicated that VEGF-stimulated angiogenesis was significantly inhibited by compound 2via targeting the phosphorylation of VEGFR2 and VEGFR2-mediated downstream angiogenesis signaling pathways. Therefore, this report demonstrates that andrographolide derivative(s) can be developed into therapeutic agent(s) against excessive angiogenesis, including tumor angiogenesis, after further improvement of the potency and stability of this series of andrographolide derivatives.

DOI10.1039/c6ra16758f
URLView the original
Language英语
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000387726500002
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China
2.School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211816, Jiangsu, China
Recommended Citation
GB/T 7714
Dekuan Sheng,Jingjing Li,Kun Wang,et al. Differential: In vitro and in vivo anti-angiogenic activities of acetal and ketal andrographolide derivatives in HUVEC and zebrafish models[J]. RSC Advances,2016,6(105):102831-102842.
APA Dekuan Sheng.,Jingjing Li.,Kun Wang.,Yuran Peng.,Shang Li.,...&Guo-Chun Zhou.(2016).Differential: In vitro and in vivo anti-angiogenic activities of acetal and ketal andrographolide derivatives in HUVEC and zebrafish models.RSC Advances,6(105),102831-102842.
MLA Dekuan Sheng,et al."Differential: In vitro and in vivo anti-angiogenic activities of acetal and ketal andrographolide derivatives in HUVEC and zebrafish models".RSC Advances 6.105(2016):102831-102842.
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