title: 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 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.
authors.affiliation: A. N. Nesmeyanov Institute of Organoelement Compounds, 28 Vavilov Street, 119991 Moscow, Russia. olshevsk@ineos.ac.ru
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Ol'shevskaya
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Zaitsev
authors.forename: Valentina N
authors.initials: VN
authors.lastname: Luzgina
authors.forename: Tatyana T
authors.initials: TT
authors.lastname: Kondratieva
authors.forename: Oleg G
authors.initials: OG
authors.lastname: Ivanov
authors.forename: Elena G
authors.initials: EG
authors.lastname: Kononova
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Petrovskii
authors.forename: Andrei F
authors.initials: AF
authors.lastname: Mironov
authors.forename: Valery N
authors.initials: VN
authors.lastname: Kalinin
authors.forename: Johann
authors.initials: J
authors.lastname: Hofmann
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Shtil
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000633:toxicity*; D001896:Boron Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*
chemical_list: C509964:5,10,15,20-tetraphenylporphyrin; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001896:Boron Compounds; D011166:Porphyrins