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

• DOI: 10.1016/j.bmc.2005.07.067
• Publication Date: 2005-09-27T14:19:28Z
• Authors: Valentina A. Ol’s...; Andrei V. Zaitsev; Valentina N. Luzgina; Tatyana T. Kondra...; Oleg G. Ivanov; Elena G. Kononova; Pavel V. Petrovskii; Andrei F. Mironov; Valery N. Kalinin; Johann Hofmann; Alexander A. Shtil
• Keywords: Boron Compounds; Porphyrins; Drug Resistance, Neoplasm; Cell Line, Tumor; Humans; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; 01 natural sciences; 0104 chemical sciences; 3. Good health

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 Bu4NF 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 (IC50 approximately 5 microM after 48-72 h of exposure) but was inert for non-malignant fibroblasts at up to 100 microM. At low micromolar concentrations, this compound caused the death of cells that express P-glycoprotein and other mechanisms of resistance to conventional anticancer drugs.