TY - JOUR
T1 - Metalloprobes
T2 - Synthesis, characterization, and potency of a novel gallium(III) complex in human epidermal carcinoma cells
AU - Harpstrite, Scott E.
AU - Prior, Julie L.
AU - Rath, Nigam P.
AU - Sharma, Vijay
N1 - Funding Information:
We thank Prof. David Piwnica-Worms for inspiring and helpful discussions and Silvia D. Collins for technical assistance. Financial assistance to this work was provided by grants from the National Institutes of Health in parts by P50 CA94056 and AI45640. Finally, funding from the National Science Foundation (MRI, CHE-0420497) for the purchase of ApexII diffractometer is also acknowledged.
PY - 2007/10
Y1 - 2007/10
N2 - 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.
AB - 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.
KW - Cytotoxicity
KW - Gallium(III) complex
KW - MDR1 P-glycoprotein
KW - Metalloprobes
UR - https://www.scopus.com/pages/publications/34548399452
U2 - 10.1016/j.jinorgbio.2007.04.013
DO - 10.1016/j.jinorgbio.2007.04.013
M3 - Article
C2 - 17617464
AN - SCOPUS:34548399452
SN - 0162-0134
VL - 101
SP - 1347
EP - 1353
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 10
ER -