Novel boronated derivatives of 5,10,15,20-tetraphenylporphyrin: Synthesis and toxicity for drug-resistant tumor cells

Abstract We have developed the synthesis of boronated porphyrins for potential application in cancer treatment, based on the functional derivatives of 5,10,15,20-tetraphenylporphyrin. Boronated amide derivatives starting from 5,10,15,20-tetra( p -aminophenyl)porphyrin and 9- o - and 9- m -carborane carboxylic acid chlorides were prepared. Also, the reaction of 2-formyl-5,10,15,20-tetraphenylporphyrin with closo -C-lithium- o - and m -carboranes, as well as with closo- C-lithium monocarbon carborane, yielded neutral and anionic boronated hydroxy derivatives of 5,10,15,20-tetraphenylporphyrin, respectively. Water-soluble forms of neutral compounds were prepared by deboronation of closo -polyhedra with Bu 4 NF into nido -7,8- and nido -7,9-dicarbaundecaborate anions. Monocarbon carborane conjugated with copper (II) complex of 5,10,15,20-tetraphenylporphyrin was active for a variety of tumor cell lines (IC 50 ∼5 μM after 48–72 h of exposure) but was inert for non-malignant fibroblasts at up to 100 μM. At low micromolar concentrations, this compound caused the death of cells that express P-glycoprotein and other mechanisms of resistance to conventional anticancer drugs.