Functionalization of cyclotriveratrilene with tetrazole and phenothiazine for doxorubicin coordination and delivery

We successfully synthesized cyclotriveratrilene functionalized with the hydrophilic heterocycles tetrazole and phenothiazine, which are commonly used to modify drug molecules. We examined their ability to coordinate doxorubicin in a dimethyl sulfoxide/water solvent mixture. For the tetrazole derivative, coordination was confirmed using proton nuclear magnetic resonance, Nuclear Overhauser Effect spectroscopy, and Ultraviolet - Visible spectroscopy. The resulting coordination complex was evaluated in breast cancer cells and exhibited higher cytotoxicity than pure doxorubicin. By contrast, the phenothiazine derivative did not exhibit any coordination capability toward the anthracycline drug and did not display cytotoxicity in cancer cells. Overall, we demonstrated that cyclotriveratrilene, when appropriately functionalized, can serve as a drug delivery system.