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

Abstract

Multidrug resistance (MDR) mediated by overexpression of the MDR1 gene product, Pglycoprotein (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 of the naphthol-Schiff base ligand (5). 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 LC 50 (the half-maximal cytotoxic concentration) value of 1.93 μM in drug-sensitive (Pgp−) cells, the gallium(III) complex 5 demonstrated an LC 50 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.

Anticancer activity of dinuclear gallium(III) carboxylate complexes

“…Gallium compounds present higher IC 50 values than that of cisplatin, however, the obtained values are comparable to those reported for other gallium complexes [38].…”

“…Therefore, many studies on the application of gallium complexes bearing chelating N,N-N,O-and O,O-donor ligands such as alkoxo-aminoand imino-groups have been carried out [30][31][32][33][34][35][36][37][38][39][40]. These chelating ligands, stabilize gallium against hydrolysis, and therefore increase the anticancer activity.…”

Novel gallium(III) complexes containing phthaloyl derivatives of neutral aminoacids with apoptotic activity in cancer cells

“…Therefore, many studies on the application of gallium complexes bearing N-, O-or S-donor ligands in anticancer tests have been carried out [28][29][30][31][32][33][34][35][36][37][38], in order to find suitable ligands that stabilize gallium against hydrolysis increasing the cytotoxicity in cancer cells. From all these complexes, carboxylate gallium(III) compounds are missing, and only structural properties regarding these compounds have been reported [39][40][41][42][43][44].…”

Metallomics related to gallium compounds: biochemical and xenobiochemical aspects

“…Radiolabeled analogues of this complex could be useful in noninvasive imaging of Pgp-mediated transport in vivo [52].…”