Boron-Containing Protoporphyrin IX Derivatives and Their Modification for Boron Neutron Capture Therapy: Synthesis, Characterization, and Comparative In Vitro Toxicity Evaluation

A novel series of boronated porphyrins for potential use in boron neutron capture therapy (BNCT) and photodynamic therapy (PDT) for tumor suppression is described. Protoporphyrin IX {i.e., bis(α‐methyl‐β‐pentylethylether)protoporphyrin IX, and bis(α‐methyl‐β‐dodecanylethylether)protoporphyrin IX} bearing polyhedral borane anions (B12H11SH2−, B12H11NH3−, or B12H11OH2−) were synthesized with reasonable yields. Modification of the protoporphyrin IX structure was achieved by variation of the lengths of the alkyl chains (pentyl and dodecanyl) attached through ether linkages to the former vinyl groups. The goal of this modification was to develop boronated porphyrins with chemical and physical properties that differed from those of protoporphyrin IX. Performance of an MTT assay with each derivative revealed that the synthesized boronated porphyrins showed low cytotoxicities in a variety of cancer cells. Of these compounds, B12H11NH22−‐conjugated porphyrin induced a significant increase in the level of boron accumulation and PDT efficacy against HeLa cells. Prodrugs: A new series of natural boronated protoporphyrins with systematically varied properties was prepared. The differences in the natures of the covalent bonds between the porphyrin and the borate anion components, as well as in the lengths of the alkoxy chain linkages to the former vinyl groups of protoporphyrin IX resulted in molecules that exhibited a wide spectrum of water solubility.