UPTAKE BY CELLS AND PHOTOSENSITIZING EFFECTIVENESS OF NOVEL PHEOPHORBIDE DERIVATIVES IN-VITRO

Pheophorbide a prepared from the algae Spirulina was derivatized at th e C(7)-carboxylic group by linking amino alkyls of various lengths and terminal functional groups. The compounds were purified by thin-layer chromatography (TLC) and by high-pressure liquid chromatography (HPLC ). Solubilization of compounds by serum lipoproteins, the kinetics of compound uptake into mammalian cells, and photosensitizing effectivene ss when activated by 673 nm laser light have been studied. Optimal pho tosensitizer uptake into cells and the greatest photosensitizing activ ity were observed with compounds having side-chain lengths of 4-6 carb on atoms which terminated in -OH and -CH3 groups. The most effective c ompounds were 3 orders of magnitude more potent than Photofrin in the degree of photoinactivation of cultured EMT-6 tumor cells. HDL and LDL significantly promoted the efflux of these photosensitizing drugs fro m cells, suggesting that their long-term retention in normal tissues i n vivo would be minimal and produce little phototoxicity. (C) 1995 Wil ty-Liss, Inc.