Commercially available taxoids demonstrate poor water solubility, present little selectivity for carcinogenic cells, and often lead to the development of multi-drug resistance phenomena. This project was designed to demonstrate the potential for a new anti-cancer drug to achieve better targeting of cancer cells, increased water solubility, and complementary cytotoxic effects.

The target molecule consists of two cytotoxic moieties, a taxoid and Chlorin A connected through a linker. The taxoid demonstrates excellent activity against several cancer cell-lines but has poor water solubility, while Chlorin A is a porphyrin that selectively targets cancer cells and becomes cytotoxic after photoactivation. The linker is a modified naturally occurring amino-acid (sarcosine or glutamic acid) and it has the role to increase the water solubility and bioavailability of the molecule. Also, the hydroxyl group in 2' position of the taxoid moiety will be esterified using N,N-dimethyl-2-aminoacetic acid for the same purpose, i.e. increased water solubility of the final compound.

The synthesis of the target molecule is extremely complex and can be divided in three parts: synthesis of the taxoid moiety; synthesis of the linker; attachment of the porphyrin core. After intravenous administration of the conjugate the porphyrin will selectively target the tumoral tissue and after internalisation and linker hydrolysis, the two cytotoxic moieties will act independently by the two complementary mechanisms described above. Biological testing will follow to examine cytotoxicity, bioavailability and potential therapeutic use of the conjugate synthesized.