Research Papers:

Discovery of DEBIC to correlate P-selectin inhibition and DNA intercalation in cancer therapy and complicated thrombosis

Haiyan Chen, Wenjing Wang, Xiaoyi Zhang, Shan Liu, Yaonan Wang, Haimei Zhu, Jianhui Wu, Yuji Wang, Ming Zhao and Shiqi Peng _

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Oncotarget. 2018; 9:32119-32133. https://doi.org/10.18632/oncotarget.23151

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Haiyan Chen1, Wenjing Wang1, Xiaoyi Zhang1, Shan Liu1, Yaonan Wang1, Haimei Zhu1, Jianhui Wu1, Yuji Wang1, Ming Zhao1,2 and Shiqi Peng1

1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, of Capital Medical University, Beijing, China

2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan

Correspondence to:

Shiqi Peng, email: sqpeng@bjmu.edu.cn

Ming Zhao, email: mingzhao@bjmu.edu.cn

Keywords: dimethyl bisindolediacetate; anti-tumor; anti-thrombosis; P-selectin; d(CGATCG)2

Received: August 30, 2017     Accepted: November 16, 2017     Epub: December 08, 2017     Published: August 14, 2018


Arterial thrombosis is one of the major complications of cancer and can seriously worsen the prognosis of the patients. These clinical findings encouraged this paper to correlate P-selectin inhibition and DNA intercalation in cancer therapy and complicated thrombosis. By designing and docking 12 derivatives of bisindole- 2-carboxylic acids into the active sites of P-selectin and d(CGATCG)2 9 derivatives were assigned to receive in vivo anti-tumor assay, and finally provided dimethyl 2,2'-[(2,2'-(ethane-1,1-diyl)bis(1H-indole-3,2-diyl)]diacetate (DEBIC) to receive assays. DEBIC intercalated DNA and inhibited proliferation of tumor cells but not non-tumor cells. It slowed tumor growth of S180 mice at a dose of 0.36 μmol/kg, and slowed tumor growth of A549 bearing BABL/C mice at a dose of 8.9 μmol/kg. DEBIC was also found to inhibit arterial thrombosis by down regulating P-selectin effectively at a dose of 0.36 μmol/kg.

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