Metalloprobes: Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells

Scott E. Harpstrite, Julie L. Prior, Nigam P. Rath, Vijay Sharma

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Multidrug resistance (MDR) mediated by overexpression of the MDR1 gene product, P-glycoprotein (Pgp), represents one of the best characterized barriers to chemotherapeutic treatment in cancer and may be a pivotal factor in progression of Alzheimer's disease (AD). Thus, agents capable of probing Pgp-mediated transport could be beneficial in biomedical imaging. Herein, we synthesized and structurally characterized a gallium(III) complex (5) of the naphthol-Schiff base ligand. The crystal structure revealed octahedral geometry for the metallodrug. Cytotoxicity profiles of 5 were evaluated in KB-3-1 (Pgp-) and KB-8-5 (Pgp+) human epidermal carcinoma cell lines. Compared with an LC50 (the half-maximal cytotoxic concentration) value of 1.93 μM in drug-sensitive (Pgp-) cells, the gallium(III) complex 5 demonstrated an LC50 value > 100 μM in drug-resistant (Pgp+) cells, thus indicating that 5 was recognized by the Pgp as its substrate, thereby extruded from the cells and sequestered away from their cytotoxic targets. Radiolabeled analogues of 5 could be beneficial in noninvasive imaging of Pgp-mediated transport in vivo.

Original languageEnglish
Pages (from-to)1347-1353
Number of pages7
JournalJournal of Inorganic Biochemistry
Volume101
Issue number10
DOIs
StatePublished - Oct 2007

Keywords

  • Cytotoxicity
  • Gallium(III) complex
  • MDR1 P-glycoprotein
  • Metalloprobes

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