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

Abstract

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 H-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.