Probing the interaction of bisintercalating (2,2′:6′,2″-terpyridine)platinum(II) complexes with glutathione and rabbit plasma

Influence of Ligand and Nuclearity on the Cytotoxicity of Cyclometallated C^N^C Platinum(II) Complexes

“…[31][32][33][34] Compounds 2 and 3 were furtherc haracterized by single crystal X-ray diffraction and both complexes were confirmed to crystallize in the same crystal space group as the published literature structures. [31,34] Additionally, 6 was characterized by 1 H, 13 C{ 1 H} and 31 P{ 1 H} NMR spectroscopy,m ass spectrometry,m elting point analysis, FTIR spectroscopy and single crystal X-ray diffraction. As inglet resonance is observed in the 31 P{ 1 H} NMR spectrum of 6 at d 20.3 ppm (J PPt = 4960Hz) and is due to the two phosphines coupling with the platinum centresi nt his symmetric molecule.…”

“…[12] Following on from this initial work, severalg roups have demonstrated the significant antiproliferative properties of platinum(II)-terpy systems,w ith reportso ft he biological activity rivalling that of cisplatin in ad iverse array of human cancer cell lines. [13][14][15][16][17][18] However,t he cytotoxicity of cyclometallated, C^N^C platinum(II) compounds has not been widely studied. [19,20] Klein and co-workers showed that as eries of cyclometallated complexesb ased on [(C^N^C)Pt II (L)],w herein C^N^C is at ridentate dianionicc yclometallating motif bearing ar ange of aryl groups;i ncluding phenyl, naphthyl and dibenzoacridine derivativesa nd L = DMSO or acetonitrile (MeCN), displayedg ood to moderate cytotoxicity againsth uman cell lines;c olorectala denocarcinoma (HT-29) and breast adenocarcinoma (MDA-MB-231).…”

“…Early reports from Lowe and co‐workers outlined the potent cytotoxicity of cyclometallated platinum(II)‐complexes incorporating a N^N^N terpyridine (terpy) ligand scaffold, and a range of N ‐heterocycles and thiolates in the fourth coordination site, against a panel of human cancer cell lines including two human ovarian carcinomas, A2780 and A2780cisR [12] . Following on from this initial work, several groups have demonstrated the significant antiproliferative properties of platinum(II)‐terpy systems, with reports of the biological activity rivalling that of cisplatin in a diverse array of human cancer cell lines [13–18] . However, the cytotoxicity of cyclometallated, C^N^C platinum(II) compounds has not been widely studied [19, 20] .…”

Integrative Metallomics Studies of Toxic Metal(loid) Substances at the Blood Plasma–Red Blood Cell–Organ/Tumor Nexus

“…Conceptually related to the application of SEC-ICP-AES to probe the stability of metallodrugs and novel metal complexes in plasma, this metallomics tool has also allowed researchers to visualize the deliberate modulation of the metabolism of cisplatin in human plasma by D-methionine [127], N-acetyl-L-cysteine [128] and sodium thiosulfate [129], which revealed that these SMW sulfur compounds can be used to 'neutralize' a highly toxic cisplatin hydrolysis product that is largely responsible for the severe side-effects of this Pt drug [130]. Thus, metallomics tools can be employed to obtain insight into the time-dependent in vitro metabolism of novel metal complexes in blood plasma, which is useful not only to estimate how much of the administered anticancer metal complex is likely to reach the cancer tissue intact [12,63], but also to gain insight into the formation of degradation products that may cause undesirable severe side-effects at the organ level [130,131].…”

The cisplatin/serum albumin system: A reappraisal

“…To this end, the advent of metallomics tools which allow one to probe the dynamic changes after cisplatin ̶ or any metal-based drug for that matter ̶ is administered into the bloodstream has emerged as a valuable approach in the quest to develop novel metal-based drugs that may offer better selectivity and fewer side effects. While it is logistically challenging to conduct such studies in whole animals, metallomics tools can be conveniently applied to probe the fate of novel metal-based drugs in human plasma in vitro [34], which makes the aforementioned proposition quite attractive today. Over the past 15 years a large variety of liquid chromatography-based metallomics approaches have been systematically developed to facilitate the analysis of complex biological fluids for endogenous metalloproteins [35][36][37].…”