Novel boronated derivatives of 5,10,15,20-tetraphenylporphyrin: synthesis and toxicity for drug-resistant tumor cells.
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.
Ol'shevskaya
Valentina A
VA
A. N. Nesmeyanov Institute of Organoelement Compounds, 28 Vavilov Street, 119991 Moscow, Russia. olshevsk@ineos.ac.ru
Zaitsev
Andrei V
AV
Luzgina
Valentina N
VN
Kondratieva
Tatyana T
TT
Ivanov
Oleg G
OG
Kononova
Elena G
EG
Petrovskii
Pavel V
PV
Mironov
Andrei F
AF
Kalinin
Valery N
VN
Hofmann
Johann
J
Shtil
Alexander A
AA
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*
C509964:5,10,15,20-tetraphenylporphyrin; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001896:Boron Compounds; D011166:Porphyrins