Antitumor properties of five-coordinate gold(III) complexes bearing substituted polypyridyl ligands

The anticancer effect related to disturbances in redox balance on Caco-2 cells caused by an alkynyl gold(I) complex

“…2B). The value obtained in the experiment for the binding constant at room temperature of 7.21·10 4 M − 1 is notably higher than the measured in the interaction of cisplatin with HSA 8.52·10 2 M − 1 [48] and in related alkyne gold(I) derivatives (values ranging from 10 1 to 10 3 ) [49], but is next to the values found in the anion [Au(CN) 2 ] − [50] and in gold(III) complexes (10 4 -10 5 ) [51,52], although significantly smaller than the observed in gold nanoparticles (around 10 8 -10 10 ) [53,54]. The experimental value of K b of 7.21·10 4 M − 1 is in accordance with a significant interaction with BSA, which would allow the biodistribution of the drug in plasma.…”

Antitumor Activity of a Polypyridyl Chelating Ligand: In Vitro and In Vivo Inhibition of Glioma

“…Previously, SBP was found to have remarkable in vitro activity against a panel of three head-neck and two lung tumor lines, and when tested against a cisplatin-resistant tumor was found to have an IC 50 value approximately 100 times lower than cisplatin ( Sanghvi et al., 2013 ). The prime mechanism of cisplatin is thought to be intercalation of DNA ( Komor and Barton, 2013 ).…”

“…In a recent study of a gold(III) complex bearing the 2,9-di- sec -butyl-1,10-phenanthroline (SBP; see Scheme 1) polypyridyl ligand, control experiments found that the free SBP ligand exhibited remarkable in vitro activity against a variety of head-neck and lung (A549 and H1703 lung, and 886LN, Tu212, and Tu686 head/neck) cancer lines. In particular, the study revealed that SBP had in vitro IC 50 values in the nanomolar concentration range, which were 20 to 100 times lower than the commonly used chemotherapy cisplatin (See Scheme 1) and 4 to 14 times lower than the parent gold(III) complex ( Sanghvi et al., 2013 ). Thus, although metals complexed to phenanthroline-based ligands continue to be investigated for their antitumor properties ( Narla et al., 2001 ; Scharwitz et al., 2008 ; Bieda, Ott, Gust, et al., 2009a ; Bieda, Ott, Dobroschke, et al., 2009b ; Dobroschke et al., 2009 ; Tan et al., 2010 ; Komor and Barton, 2013 ), our understanding of the properties and potential chemotherapeutic action of the ligands themselves remains an unexplored area of research.…”

“…One important finding in regard to the antitumor efficacy of SBP was that it had significant activity against the cisplatin-resistant H1703 lung tumor cell line, suggesting that SBP likely initiates tumor cell death via a mechanism involving a non-DNA target ( Sanghvi et al., 2013 ). To date, the most successful drugs for treatment of glioblastoma, including TMZ, have been lipophilic alkylating agents that disrupt tumor cell growth through processes that initiate DNA damage ( Ajaz et al., 2014 ).…”

“…Though platinum-based drugs have had more limited success in vivo , novel drug delivery approaches for glioblastoma treatment are being pursued ( Charest et al., 2013 ; Miura et al., 2013 ). Given the aforementioned activity of SBP against cisplatin-resistant tumor cells, and the fact SBP is hypothesized to have non-DNA intracellular targets ( Sanghvi et al., 2013 ), it was of interest to determine if this drug might have potential as a new lead compound for glioblastoma treatment. In particular, it was desired to determine whether a compound with a potentially different mechanism of antitumor activity might show promise as a therapeutic against glioblastoma tumors.…”