Citation: Guo Liang, Xie Jianwei, Fan Wenxi, Chen Wei, Dai Bin, Ma Qin. Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer[J]. Chinese Journal of Organic Chemistry, ;2017, 37(7): 1741-1747. doi: 10.6023/cjoc201701005 shu

Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

Guo Liang ^a,b ,
Xie Jianwei ^a,b ,
Fan Wenxi ^c ,
Chen Wei ^c ,
Dai Bin ^a,b,, ,
Ma Qin ^c

a.
School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003
b.
Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, Shihezi 832003
c.
Xinjiang Huashidan Pharmaceutical Research Co., Ltd., Urumqi 830011

Corresponding author: Dai Bin, db_tea@shzu.edu.cn
Received Date: 4 January 2017
Revised Date: 7 March 2017
Available Online: 17 July 2017
Fund Project: Program for Outstanding Youth Science and Technology Innovation Talents Training in Xinjiang Uygur Autonomous Region qn2015jc067Project supported by the Program for Outstanding Youth Science and Technology Innovation Talents Training in Xinjiang Uygur Autonomous Region (No.qn2015jc067)

Figures(3)

In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substituted bivalent β-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by ¹H NMR, ¹³C NMR, and HRMS. The cytotoxic activities of all bivalent β-carbolines were evaluated in vitro against a panel of human tumor cell lines (22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, HepG-2, A375, and 769-P) and compared with the positive control cisplatin and monovalent β-carbolines. The results demonstrated that compounds 5a~5h exhibited potent cytotoxic activities with IC₅₀ values lower than 10 μmol·L^-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC₅₀ values of 0.8 μmol·L^-1 and 0.6 μmol·L^-1, respectively.
- bivalent β-carboline,
- synthesis,
- antitumor activity,
- structure-activity relationship
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