The supramolecular self-assembly of 5-fluorouracil and caffeic acid through cocrystallization strategy opens up a new way for the development of synergistic antitumor pharmaceutical cocrystal

摘要: In order to give full play the superiority of cocrystallization techniques overcome biopharmaceutical limitations in vitro and ameliorate pharmacokinetic properties vivo together with heightening antitumor abilities anticancer drug 5-fluorouracil (FL), gain some further insights into development novel pharmaceutical cocrystals synergetic activity between an active ingredient former cocrystal, a new cocrystal FL caffeic acid (CF), namely FL-CF-2H2O, has been successfully exploited systematically studied. Single-crystal X-ray diffraction analysis confirms that asymmetric unit newly synthesized consists one FL, CF two solvent water molecules, which complementary molecules compose planar hydrogen-bonding pair. Water fill hole surrounded by three arrays pairs link each other via hydrogen bonds form three-dimensional supramolecular network, is reinforced aromatic packing interactions. The characteristics are evaluated through combination theoretical experimental methods. It found permeability solubility from FL-CF-2H2O synchronously enhanced relative pure supported molecular electrostatic potential calculation Hirshfeld surface analysis. Interestingly, ameliorated can efficaciously change optimized pharmacokinetics prolonged half-life increased bioavailability compared itself. What even more interesting exhibit synergistic effects on tested cell lines. Thus, this work not only provides crystalline for application prospects, but also initiates intelligent idea cocrystals.