Synthesis of curcumin deriva atives as anti-tumor agents

Abstract

Curcumin is a natural phenolic compound with diverse pharmacological activities and shows synergism effect with paclitaxel in killing cancer cells. However, the compound’s low aqueous solubility and instability in physiological conditions have limited its application. Here water dispersible methoxy poly (ethylene oxide)-palmitate-curcumin conjugate (mPEO-CUR-PA) was synthesized by reacting curcumin with palmitic anhydride to give palmitoyl curcumin(CUR-PA), followed by coupling and coupling with methoxypoly (ethylene oxide) acetic acid (mPEO-COOH) obtained via succinylation of methoxypoly(ethylene oxide). The products could automatically self-assemble into water dispersible microspheres which by themselves showed better anti-tumor activity than free curcumin. The endocytosis of the microspheres into cancer cells was witnessed by confocal laser fluorescent microscope. Paclitaxel could be loaded into the obtained microspheres, and the paclitaxel-loaded mPEO-CUR-PA showed the increasing of anti-tumor activity in both the wild type and the paclitaxel-resistant cancer cells when compared to the activity of free paclitaxel.