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Design and synthesis of furozan-based nitric oxide-releasing derivatives of oridonin with anti-proliferative activity
LI Dahong 1 #,WANG Lei 2,CAI Hao 1,WU Xiaoming 2,SUN Yijun 1,XU Jinyi 2 *
1.Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009
2.State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009
*Correspondence author
#Submitted by
Subject:
Funding: Specialized Research Fund for the Doctoral Program of Higher Education (No.No. 20100096110001), the Fundamental Research Funds for the Central Universities (No.JKY2011030), Project for Research and Innovation of Graduates in Universities of Jiangsu Province (No.CXZZ11-0800), National Natural Science Fund (No.No. 30973610)
Opened online: 9 July 2012
Accepted by: none
Citation: LI Dahong,WANG Lei,CAI Hao.Design and synthesis of furozan-based nitric oxide-releasing derivatives of oridonin with anti-proliferative activity[OL]. [ 9 July 2012] http://en.paper.edu.cn/en_releasepaper/content/4483697
 
 
To search for novel nitric oxide (NO) releasing anti-tumor agents, a series of novel furoxan/oridonin hybrids were designed and synthesized. Firstly, the nitrate/nitrite levels in the cell lysates were tested by Griess assay and the results showed that these furoxan-based NO-releasing derivatives could produce high level of NO in vitro. Then the anti-proliferative activity of these hybrids against four human cancer cell lines were also determined, among which, 9h exhibited the most potential anti-tumor activity with IC50 values of 1.82 μM against K562, 1.81μM against MGC-803 and 0.86 μM against Bel-7402, respecively. Structure-activity relationship was concluded based on the experimental data obtained. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.
Keywords:NO-donor; oridonin; hybrid; anti-tumor activity; SAR
 
 
 

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