Synthesis and biological evaluation of novel alkyl diamine linked bivalent β-carbolines as angiogenesis inhibitors

Eur J Med Chem. 2016 Nov 29:124:249-261. doi: 10.1016/j.ejmech.2016.08.050.

Wei Chen ¹, Guoxian Zhang ², Liang Guo ¹, Wenxi Fan ¹, Qin Ma ¹, Xiaodong Zhang ³, Runlei Du ⁴, Rihui Cao ⁵

Affiliations

1 Xinjiang Huashidan Pharmaceutical Co. Ltd., 45 He Nan East Road, Urumqi 830011, PR China.
2 School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
3 College of Life Sciences, Wuhan University, 299 Ba Yi Road, Wuchang 430072, PR China.
4 College of Life Sciences, Wuhan University, 299 Ba Yi Road, Wuchang 430072, PR China. Electronic address: runleidu@163.com.
5 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.

PMID: 27592394 DOI: 10.1016/j.ejmech.2016.08.050

Abstract

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 IC₅₀ value 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.

Keywords

Angiogenesis inhibitors; Antitumor; Bivalent β-carbolines; Structure-activity relationships; Synthesis.

Name
Email *

	Sorry, but the email address you supplied was invalid.