Probing the Interactions of Cytotoxic [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)] and Its Pt Derivatives with Human Serum.

The discrepancy between the in vitro cytotoxic results and the in vivo performance of Pt56MeSS prompted us to look into its interactions and those of its Pt derivatives with human serum (HS), human serum albumin (HSA), lipoproteins, and serum-supplemented cell culture media. The Pt complex, Pt56MeSS, binds noncovalently and reversibly to slow-tumbling proteins in HS and in cell culture media and interacts through the phenanthroline group with HSA, with a K value of ∼1.5×10  m.

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

Platinum(II) complexes have demonstrated considerable success in the treatment of cancer, but severe toxic side effects drive the search for new complexes with increased tumour selectivity and better efficacy. A critical concept that has to be considered in the context of designing novel Pt complexes is their interactions with biomolecules other than DNA. To this end, here the interactions of 16 previously reported bisintercalating (2,2':6',2″-terpyridine)platinum(II) complexes, [{Pt(terpy)}μ-(X)] (where X is a linker) with glutathione (GSH) by means of H and Pt NMR spectroscopy were investigated.

Quadruplex DNA-Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers.

Four dinuclear terpyridineplatinum(II) (Pt-terpy) complexes were investigated for interactions with G-quadruplex DNA (QDNA) and duplex DNA (dsDNA) by synchrotron radiation circular dichroism (SRCD), fluorescent intercalator displacement (FID) assays and fluorescence resonance energy transfer (FRET) melting studies. Additionally, computational docking studies were undertaken to provide insight into potential binding modes for these complexes. The complexes demonstrated the ability to increase the melting temperature of various QDNA motifs by up to 17 °C and maintain this in up to a 600-fold excess of dsDNA.

The synthesis, characterisation and cytotoxicity of bisintercalating (2,2':6',2''-terpyridine)platinum(II) complexes.

Dinuclear (2,2':6',2''-terpyridine)platinum(II) (PtTerpy) complexes were synthesised by tethering either thiol or pyridine based linkers. All intermediates and resulting complexes were characterised using a combination of (1)H and (195)Pt NMR, two-dimensional (1)H correlation spectroscopy (NOSY/COSY), two-dimensional (1)H/(195)Pt heteronuclear multiple bond correlation spectroscopy (HMQC), elemental analysis and electrospray ionisation mass spectrometry (ESI-MS). The cytotoxicity of the complexes was determined against human A2780 ovarian carcinoma cells and its cisplatin-resistant sub-line A2780cis, as well as L1210 murine leukemia cells.

Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.

With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.

The effects of 56MESS on mitochondrial and cytoskeletal proteins and the cell cycle in MDCK cells.

Background: 56MESS has been shown to be cytotoxic but the mode of this action is unclear. In order to probe the mechanism of action for 56MESS, MDCK cells were utilised to investigate the effect on treated cells.

Results: IC50 values for 56MESS and cisplatin in the MDCK cell line, determined by a SRB assay, were 0.

Transition metal based anticancer drugs.

With an ageing baby-boomer population in the Western World, cancer is becoming a significant cause of death. The prevalence of cancer and all associated costs, both in human and financial terms, drives the search for new therapeutic drugs and treatments. Platinum anticancer agents, such as cisplatin have been highly successful but there are several disadvantages associated with their use.

Advances in platinum chemotherapeutics.

The approved platinum(II)-based anticancer agents cisplatin, carboplatin and oxaliplatin are widely utilised in the clinic, although with numerous disadvantages. With the aim of circumventing unwanted side-effects, a great deal of research is being conducted in the areas of cancer-specific targeting, drug administration and drug delivery. The targeting of platinum complexes to cancerous tissues can be achieved by the attachment of small molecules with biological significance.