Synthesis of Anthraquinone-Ibuprofen Prodrugs with Hydroxyapatite Affinity and Anti-Inflammatory Activity Characteristics

The synthesis and pharmacological activities of anthraquinone-ibuprofen prodrugs for finding new anti-inflammatory drugs specifically targeting osseous tissues were studied. Two hydrolytically activated anti-inflammatory prodrugs containing anthraquinone moiety and ibuprofen moiety were designed and synthesized. Rhein was chosen as bone-targeting agent and potentially active drug, which was linked chemically with ibuprofen through glycol ester as bone-targeting anti-inflammatory prodrugs. The chemical structures of the new compounds were confirmed by IR, H-1 NMR, C-13 NMR, MS and elemental analysis. The studies of bioactivities demonstrated that both prodrugs showed significant binding capability to hydroxyapatite (HAP), the major component of bone, and were hydrolytically activated under physiological conditions in vitro and better anti-inflammatory activity in vivo.