Synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors.
We have synthesized and evaluated a series of novel alkyl diamine linked bivalent β-carbolines as potent angiogenesis inhibitors. The results demonstrated that most bivalent β-carbolines exhibited significant antiproliferative effects against human umbilical vein cell lines EA.HY926. Compound 4m was found to be the most potent antiproliferative agent with IC50value of 2.16 μM against EA.HY926 cell lines. Mechanism investigations revealed that compound 4m could significantly inhibit EA.HY926 cells migration and tube formation in a dose-dependent manner. Moreover, compound 4m also showed obvious angiogenesis inhibitory effects in CAM assay, and the antiangiogenetic potency was more potent than the reference drug Endostar. The bivalent β-carbolines might be served as candidates for the development of vascular targeting antitumor drugs.
Xinjiang Huashidan Pharmaceutical Co. Ltd., 45 He Nan East Road, Urumqi 830011, PR China.
Wei
W
Chen
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Guoxian
G
Zhang
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.
Wenxi
W
Fan
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*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003959:Diamines / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D002243:Carbolines; D003959:Diamines
Angiogenesis inhibitors; Antitumor; Bivalent β-carbolines; Structure-activity relationships; Synthesis