Design, synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors.
A series of novel alkyl diamine linked bivalent β-carbolines was synthesized and evaluated for antiproliferative activity, inhibition of cell migration and tube formation, and anti-angiogenic activity in vivo. The results showed that most bivalent β-carbolines displayed significant antiproliferative effect against human umbilical vein cell lines EA.HY926. Compound 2s was found to be the most potent antiproliferative agent with IC50value of 1.06μM against EA.HY926 cell lines. Further investigations on mechanisms of action revealed that compound 2s significantly inhibited EA.HY926 cells migration and tube formation in a dose-dependent manner. Moreover compound 2s exhibited significant angiogenesis inhibitory effects in CAM assay, and the antiangiogenetic potency was comparable with the reference drug Endostar (30μM).
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Qing
Q
Chen
Xinjiang Huashidan Pharmaceutical Co. Ltd, 45 He Nan East Road, Urumqi 830011, PR China.
Wei
W
Chen
Xinjiang Huashidan Pharmaceutical Co. Ltd, 45 He Nan East Road, Urumqi 830011, PR China.
Wenxi
W
Fan
Xinjiang Huashidan Pharmaceutical Co. Ltd, 45 He Nan East Road, Urumqi 830011, PR China.
Liang
L
Guo
Xinjiang Huashidan Pharmaceutical Co. Ltd, 45 He Nan East Road, Urumqi 830011, PR China.
Qin
Q
Ma
College of Life Sciences, Wuhan University, 299 Ba Yi Road, Wuchang 430072, PR China.
Xiaodong
X
Zhang
College of Life Sciences, Wuhan University, 299 Ba Yi Road, Wuchang 430072, PR China. Electronic address: runleidu@163.com.
Runlei
R
Du
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China. Electronic address: caorihui@mail.sysu.edu.cn.
Rihui
R
Cao
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans
D020533:Angiogenesis Inhibitors; D002243:Carbolines
Angiogenesis inhibitors; Antitumor; Bivalent β-carbolines; Structure–activity relationships; Synthesis