Dimethyl 2,2'-[2,2'-(ethane-1,1-diyl)bis(1-indole-3,2-diyl)]-diacetate: a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect.

Background: Due to the discovery that deep venous thrombosis (DVT) inhibitor is of chemotherapeutic importance, the nano-property of dimethyl 2,2'-[2,2'-(ethane-1,1-diyl) bis(1-indole-3,2-diyl)]-diacetate (DEBIC), a recently reported antitumor agent, is worthy of characterization.

Materials And Methods: One-pot reaction was used to prepare DEBIC. Electrospray Ionization (+/-)-Fourier Transform-Ion Cyclotron Resonance-Mass Spectrometer (ESI(+/-)-FT-ICR-MS), quadrupole Collision Induced Dissociation (qCID) and nuclear overhauser effect spectroscopy spectra were used to present the assembly of DEBIC. Transmission electron microscopy, scanning electron microscopy, atomic force microscopy and Faraday-Tyndall effect were used to visualize the nano-property of DEBIC. Rat models were used to evaluate DVT inhibition and the bleeding reaction of DEBIC.

Results: One-pot reaction can provide DEBIC in acceptable yield and high purity. In water, rat plasma and lyophilized powders of DEBIC existed as particles of small nano-size. In vivo DEBIC inhibited DVT in a dose-dependent manner. The minimal effective dose of DEBIC was 1.7 μmol/kg. Even the dose of 36 μmol/kg/day DEBIC did not induce bleeding side effect in DVT rats like in warfarin (0.82 μmol/kg/day).

Conclusion: DEBIC is a small molecule capable of nano-scale assembly, inhibiting venous thrombosis and inducing no bleeding side effect.