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

Authors：Chen, Haiyan; Wang, Wenjing; Zhang, Xiaoyi; Liu, Shan; Wang, Yaonan; Zhu, Haimei; Wu, Jianhui; Wang, Yuji; Zhao, Ming; Peng, Shiqi

Source：Oncotarget, 2018, 9(63): 32119-32133.

DOI：10.18632/oncotarget.23151

• P-selectin
• anti-thrombosis
• anti-tumor
• d(CGATCG)2
• dimethyl bisindolediacetate

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 mumol/kg, and slowed tumor growth of A549 bearing BABL/C mice at a dose of 8.9 mumol/kg. DEBIC was also found to inhibit arterial thrombosis by down regulating P-selectin effectively at a dose of 0.36 mumol/kg.