Corrigendum to: Recent Developments in the Field of Tumor-Inhibiting Metal Complexes.

An article was published in the journal "Current Pharmaceutical Design", Volume 9, No. 25, 2003, pp: 2078-2089 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/8545 We regret the error and apologize to readers.

Corrigendum to: The Relation Between Stereochemistry and Biological Activity of Platinum(II) Complexes Chelated with Chiral Diamine Ligands: An Intricate Problem.

An article was published in the journal "Current Pharmaceutical Design," Volume 13, No. 27, 2007, pp: 2781-2794 [1]. The first author is requesting an alteration in the name. Details of a correction are provided here. The original name published was Markus Galanski. The request is to change the name to Mathea Sophia Galanski. The original article can be found online at: https://www.eurekaselect.com/article/4836 We regret the error and apologize to readers.

Lectin conjugates as biospecific contrast agents for MRI. Coupling of Lycopersicon esculentum agglutinin to linear water-soluble DTPA-loaded oligomers.

Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer-DTPA compounds were characterised by (1)H NMR and mass spectrometry. The final lectin-DTPA-polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents.

Lectin-Gd-loaded chitosan hydrogel nanoparticles: a new biospecific contrast agent for MRI.

PURPOSE: Non-specific extracellular contrast agents have been on the market for more than 15 years. Here, we report on the synthesis of new selective lectin-gadolinium (Gd)-loaded chitosan nanoparticles with a prolonged clearance time and a much higher relaxivity in comparison to other preparations. PROCEDURES: Chitosan nanoparticles were prepared from 85% deacetylated chitin by glutaraldehyde cross-linking of an aqueous acetic acid dispersion of chitosan in a mixture of n-hexane using sodium bis(ethylhexyl)sulfosuccinate as a surfactant. RESULTS: Several crucial parameters, namely, the Gd and protein content of the nanoparticles, their size and dispersity were determined. Magnetic resonance measurements were carried out by intravenous perfusion of mono-disperse suspensions of the nanoparticles into mice. CONCLUSIONS: Chitosan nanoparticles can be used as contrast agents in magnetic resonance imaging (MRI). They are excellent candidates for controlled delivery of bioactive compounds to molecular targets and as biospecific diagnostic tools in MRI.

The Relation Between Stereochemistry and Biological Activity of Platinum(II) Complexes Chelated with Chiral Diamine Ligands: An Intricate Problem+

The origin of activity differences between stereoisomers of anticancer platinum(II) complexes chelated with chiral diamine ligands has been almost exclusively explained by diastereoselective interactions with DNA. Although this model has been widely accepted in vitro and in vivo experiments showed some conflicting results, leading to the conclusion that other biomolecules might be responsible for this stereoselectivity as well. These compounds, called bionucleophiles, are in most instances amino acids or proteins present in biological fluids. As these chiral molecules are very reactive towards the platinum complexes, they may contribute to stereoselectivity, but also to resistance and toxicity. This review gives a general survey of chiral platinum(II) complexes and their interactions with DNA. The bionucleophiles which have been identified and the consequences of their reaction with platinum(II) complexes are discussed. Analytical techniques used to investigate interactions between established and potential chiral platinum drugs and bionucleophiles are presented.

Recent Developments in the Field of Tumor-Inhibiting Metal Complexes

25 years after the first approval of cisplatin in the clinic against a number of cancer diseases, cisplatin and related compounds continue to be among the most efficient anticancer drugs used so far. Efforts are focused to develop novel platinum- and non-platinum-based antitumor drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. In the field of non-platinum compounds exhibiting anticancer properties, ruthenium complexes are very promising, showing activity on tumors which developed resistance to cisplatin or in which cisplatin is inactive. Furthermore, general toxicity was found to be very low. The first ruthenium compound NAMI-A entered phase I clinical trials in 1999 as an antimetastatic drug, whereas the ruthenium complex KP1019 will enter phase I clinical trials in 2003 as an anticancer drug which is among others very active against colon carcinomas and their metastases. Remarkable progress is also seen in developing tumor inhibiting gallium compounds. One of them, KP46, will also enter phase I clinical trials in 2003. This article reviews briefly the achievements in the field of anticancer metal complexes focusing the discussion onto the impact of the group of Bioinorganic Chemistry at the Department of Inorganic Chemistry at the University of Vienna. The development of pH sensitive platinum prodrugs, platinum-based drug targeting strategies with low-molecular-weight carriers, kinetically inert platinum(IV) complexes, as well as tumor inhibiting non-platinum anticancer drugs based on ruthenium and gallium is covered in the following sections.

Tumour-inhibiting platinum complexes--state of the art and future perspectives.

Thirty years after the onset of the first clinical studies with cisplatin, the development of antineoplastic platinum drugs continues to be a productive field of research. This article reviews the current preclinical and clinical status, including a discussion of the molecular basis for the activity of the parent drug cisplatin and platinum drugs of the second and third generation, in particular their interaction with DNA. Further emphasis is laid on the development of third generation platinum drugs with activity in cisplatin-resistant tumours, particularly on chelates containing 1,2-diaminocyclohexane (DACH) and on the promising and more recently evolving field of non-classic ( trans- and multinuclear) platinum complexes. The development of oral platinum drugs and drug targeting strategies using liposomes, polymers or low-molecular-weight carriers in order to improve the therapeutic index of platinum chemotherapy are also covered.

HPIC-UV-ICP-SFMS study of the interaction of cisplatin with guanosine monophosphate.

Interaction of cis-[Pt(NH3)2Cl2] (cisplatin) with 5'-guanosine monophosphate (5'-GMP) has been investigated for the first time by on-line coupling of high performance ion chromatography (HPIC) to inductively coupled plasma sector field mass spectrometry (ICP-SFMS). The time-dependent reaction course of the cisplatin-5'-GMP system was followed after incubation under simulated physiological conditions by monitoring the decrease in the concentration of 5'-GMP and the increase in the concentration of formed adducts, on the basis of speciation analysis. Because of the two-step mechanism an intermediate mono adduct was observed together with the major product, the bis adduct cis-[Pt(NH3)2(GMP)2]2-. The data obtained correlated well with those from earlier studies employing orthogonal techniques such as capillary electrophoresis (CE). Furthermore, HPIC-ICP-SFMS provided unambiguous stoichiometric information about the major GMP-adduct. For this purpose the platinum-to-phosphorus ratio was determined by simultaneously measuring 31P and 195Pt. To separate significant interferences from 15N16O+, 14N16O1H+, 12C18O1H+, and 13C17O1H+ on 31P, high-mass resolution (m/deltam = 4,500) proved to be mandatory. The P/Pt signal ratio of 2/1 obtained corresponds to the molar ratio in the bis adduct cis-[Pt(NH3)2(GMP)2]2-.