vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy

To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrro-methene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives tomaximize the “heavy atom effect ” or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated com-pound, while those with an iodinated BODIPY core presented better photocytotoxicity than com-pounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G2/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photo-dynamic therapy agents for cancer