Synthesis and in vitro Antitumor Potency of (Cyclohexane-1,2-Diamine)Platinum(II) Complexes with Aminotris(Methylenephosphonic Acid) as Bone-Seeking Ligand

In order to develop platinum complexes with selective activity in primary and secondary bone malignancies and with the aim to optimize antitumor activity, platinum(II) complexes with aminotris(methylenephosphonic acid) as bone-seeking (osteotropic) ligand have been synthesized, characterized and tested in the cisplatin-sensitive ovarian carcinoma cell line CH1. As non-leaving diamine ligands, which are decisive for the cellular processing of DNA adducts, cis-R,S-cyclohexane-1,2-diamine, trans-S,S-cyclohexane-1,2-diamine and trans-R,R-cyclohexane-1,2-diamine have been used, resulting in complexes 1, 2, and 3, respectively. The cytotoxicity of the complexes under investigation decreases in the order 3 > 2 > 1 which is in accord with structure-activity relationships with other (cyclohexane-1,2- diamine)platinum(II) and platinum(IV) complexes: Both trans complexes (2 and 3) display a higher in vitro potency than the corresponding cis isomer (I), with the trans-R,R isomer (3) being the most active in this series. In comparison to the analogous (cyclohexane-1,2-diamine)platinum(II) complexes with bis(phosphonomethyl)aminoacetic acid as osteotropic carrier ligand, the cytotoxicity of 1-3 was found to be 1.5 – 2 fold higher, which is explainable by a different coordination mode of the phosphonic acid ligands (acetato versus phosphonato)

Oxaliplatin reacts with DMSO only in the presence of water

Herein we show that oxaliplatin reacts rapidly with DMSO in aqueous solutions, despite being stable in pure DMSO and pure water. Furthermore, the reactivity of the clinically applied Pt(II) drugs in water/DMSO and PBS/DMSO mixtures, and the nature of the species formed were investigated by MS, NMR and RP-HPLC techniques

Maleimide-functionalised platinum(IV) complexes as synthetic platform for targeted drug delivery

Maleimide-functionalised Pt(IV) complexes with highly selective binding properties to thiol groups were synthesised as precursors for binding of thiol-containing tumour targeting molecules like human serum albumi

The impact of whole human blood on the kinetic inertness of platinum(IV) prodrugs - an HPLC-ICP-MS study

The potential advantage of platinum(IV) complexes as alternative to classical platinum(II)-based drugs relies on their kinetic stability in the body before reaching the tumor site and on their activation by reduction inside cancer cells. In this study, an analytical workflow was developed to investigate the reductive biotransformation and kinetic inertness of platinum(IV) prodrugs comprising different ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of the platinum(IV) complexes in blood pellet and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion. An analytical approach based on reversed-phase (RP)-ICP-MS was used to monitor the parent compound and the formation of metabolites using two different extraction procedures. The ligand coordination sphere of the platinum(IV) complexes had significant impact on their accumulation in red blood cells and on their degree of kinetic inertness in whole human blood. The most lipophilic platinum(IV) compound featuring equatorial chlorido ligands showed a pronounced penetration into blood cells and a rapid reductive biotransformation. In contrast, the more hydrophilic platinum(IV) complexes with a carboplatin- and oxaliplatin-core exerted kinetic inertness on a pharmacologically relevant time scale with notable amounts of the compound accumulated in the plasma fraction

Signal separation and determination of the enantiomeric purity of primary amines with (-)-myrtenal - a 13C NMR study

The applicability of (-)-myrtenal as a chiral derivatizing agent in combination with 13C NMR spectroscopy was investigated. 13C NMR was found to be a valuable tool for the identification and enantiomer differentiation of primary amines including β-amino alcohols and vicinal diamines. The enantiomeric excess could be determined via automated deconvolution and integration, and was found to be in good accordance with the expected values even in the cases, when enantiomer differentiation was not possible in 1H NMR spectra. © 2006 Elsevier B.V. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe