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Tytuł:
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Targeting the folate receptor (FR): imaging and cytotoxicity of ReI conjugates in FR-overexpressing cancer cells.
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Autorzy:
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Viola-Villegas N; Department of Chemistry, Syracuse University, Syracuse, NY 13244-4100, USA.
Rabideau AE
Cesnavicious J
Zubieta J
Doyle RP
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Źródło:
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ChemMedChem [ChemMedChem] 2008 Sep; Vol. 3 (9), pp. 1387-94.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Weinheim, Germany : Wiley-VCH, c2006-
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MeSH Terms:
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Carrier Proteins/*biosynthesis
Carrier Proteins/*drug effects
Folic Acid/*chemistry
Organometallic Compounds/*pharmacology
Ovarian Neoplasms/*drug therapy
Receptors, Cell Surface/*biosynthesis
Receptors, Cell Surface/*drug effects
Rhenium/*chemistry
Animals ; CHO Cells ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cricetinae ; Cricetulus ; DNA/chemistry ; DNA/drug effects ; DNA Topoisomerases, Type I/chemistry ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Electrophoretic Mobility Shift Assay/methods ; Female ; Folate Receptors, GPI-Anchored ; Folic Acid/analogs & derivatives ; Folic Acid/chemical synthesis ; Humans ; Inhibitory Concentration 50 ; Intercalating Agents/chemical synthesis ; Intercalating Agents/chemistry ; Intercalating Agents/pharmacology ; Microscopy, Confocal ; Molecular Structure ; Organometallic Compounds/chemical synthesis ; Organometallic Compounds/chemistry ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Reverse Transcriptase Polymerase Chain Reaction ; Structure-Activity Relationship ; Topoisomerase I Inhibitors
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Substance Nomenclature:
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0 (Carrier Proteins)
0 (Folate Receptors, GPI-Anchored)
0 (Intercalating Agents)
0 (Organometallic Compounds)
0 (Receptors, Cell Surface)
0 (Topoisomerase I Inhibitors)
7440-15-5 (Rhenium)
9007-49-2 (DNA)
935E97BOY8 (Folic Acid)
EC 5.99.1.2 (DNA Topoisomerases, Type I)
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Entry Date(s):
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Date Created: 20080725 Date Completed: 20081216 Latest Revision: 20131121
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Update Code:
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20240104
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DOI:
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10.1002/cmdc.200800125
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PMID:
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18651631
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The synthesis, characterization, in vitro imaging, and cytotoxic properties of a new folate conjugate of rhenium(I) are reported. The conjugate [FA-PEG-BQAV-Re(CO)3]+ (gamma-4) was screened against an adriamycin- and cisplatin-resistant human ovarian cancer cell line (A2780/AD) that overexpresses the folate receptor (FR). Compound gamma-4 was internalized by a folate-receptor-mediated endocytotic pathway, which results in internal accumulation of gamma-4. This was contrasted with a FR-negative Chinese hamster ovary cell line in which no internalization of gamma-4 was observed. gamma-4 was found to be cytotoxic with IC(50) values of 189 and 78 microM at 6 and 24 h, respectively, toward the FR-positive cell line. This is in contrast to the IC(50) value of 502 microM at 6 h and 84 microM at 24 h for cisplatin in the same cell line, with a significantly greater toxicity at the earlier time point. The cytotoxicity of gamma-4 as explained by interactions that occur between the rhenium(I) complex moiety and DNA is described.