The purpose of this research is to synthesize a conjuate through linkage of a porphyrin photodynamic therapeutic with a taxoid cancer chemotherapeutic. Upon entrance into the cell, the conjugate will be cleaved to release the porphyrin and the taxoid, and will thereby provide two distinct mechanisms of generating cancer cell death. Photodynamic therapy, on one hand, involves administration of a tumor-localizing photosensitizing porphyrin, followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. The second mechanism of action would be via traditional cancer chemotherapy whereby the polymerization of tubulin to form stabilized microtubles is accelerated, thus interrupting cellular mitosis, and inducing programmed cell death. The preparation of the desired taxoid-porphyrin conjugate requires the use of organic synthetic procedures. Generally, the progress of a reaction is moniotred by thin-layer chromotography, and is quenched after running to completion. The separation funnel is then used to either wash impurities from the desired product or extract desired material that has dissociated into another layer. The product mixture is subjected to a drying agent in order to remove any residue water, and then introduced into a silica gel column for further purification. The collected fractions are rotary evaporated and vacuumed to vaporize any remaining solvent. After proton nuclear magnetic resonance (1H-NMR) and high performance liquid chromotography (HPLC) results indicate acceptable final product purity, analysis of biological activity will be done using an IC50 asay. This date will represtnt the concentraiton of the compound rquired to kill half the tumor cells of an in vitro biological model.

This research was supported by Simons Foundation grant #265210 and Stony Brook Foundation grant #265790.