Platinum structure-activity relationships

Farrell, N. P. Qu, Y. Bierbach, U. Valsecchi, M. Menta, E. Structure-activity Relationships within Di- and Trinuclear Platinum Phase I Clinical Agents In Cisplatin Chemistry and Biochemistry of a Leading Anticancer Drug Lippert, B., Ed. Verlag, 1999, pp 479 196. 

The early empirical structure-activity relationships promoted discovery of second-generation anticancer drugs such as complexes 2 and 3. However, analogs of these drugs usually display similar clinical profiles to the parent drugs. Therefore new classes of platinum complexes are required with distinct properties. 

Models of adducts that link one strand of DNA to the other (interstrand) have also been produced121 2121. These, too, reveal hydrogen bonding interactions consistent with established structure-activity relationships. The models have been used to aid in the design of new platinum(II) complexes that should form the interstrand adducts in preference to intrastrand adducts12151. 

Structure-Activity Relationships Within Di- and Trinuclear Platinum Phase-I Clinical Anticancer Agents... 

Structure-Activity Relationships for Dinuclear Platinum Compounds... 

Both pyridine (pyr) and quinoline (quin) compounds are efficient cross-linking agents but not potent cytotoxic agents. Interstrand cross-linking is thus not by itself a sufficient requirement for cytotoxicity. These results were also of considerable interest because the mononuclear precursors were found to be similar in cytotoxicity to cisplatin itself, violating the classical structure-activity relationship of platinum compounds. Yet incorporation into the dinuclear structure did not produce active compounds ... 

For example, key intermediates of the catalytic CO oxidation on rhodium and on platinum at elevated pressure are not present under vacuum conditions (Somorjai and Rupprechter, 1999). These "gaps" in materials and pressure have to be bridged to establish quantitative structure-activity relationships (Topsoe, 2000 Wachs, 2003a, 2003b, 2003c). Raman spectroscopy is one of the most useful techniques for bridging these "gaps" and is the focus of this chapter. 

N. Farrell, Y. Qu, U. Bierbach, M. Valsecchi, and E. Menta, Structure-activity Relationships Within Di-and Trinuclear Platinum Phase-I Clinical Anticancer Agents, in 30 Years of Cisplatin, Chemistry and Biochemistry of a Leading Anticancer Drug , ed. B. Lippert, Wiley VCH, Weinheim, 1999, p. 479. 

Platinum Anticancer Drugs Structure-Activity Relationships and Complexes on Clinical Trials Y... 

Biologically active platinum complexes have now been under investigation for nearly two decades. The large data base on structure-activity relationships has revealed a number of principles as well as raised new questions. Mechanistically, the aquation of the compounds and their ability to cause intrastrand cross-links in defined regions of DNA appear to be the chemical events most closely associated with antitumour activity. The reaction kinetics of the compounds in aqueous systems which may be influenced by chelate effects, steric hindrance of bulky ligands or metal oxidation state have been studied for... 

A vast number of platinum compounds have now been screened for antitumor activity, and the results of these investigations have led to a set of empirical guidelines for the minimum structural features required for activity. Although they may be stated in various forms, the key structure-activity relationships... 

Structure-Activity Relationships in Polynuclear Platinum Complexes... 

Current Status of Structure-Activity Relationships of Platinum Anticancer Drugs Activation of the trans-Geometry Nicholas Farrell... 

Oszwaldowski, S. and Timeibaev, A. 2007, Developmaitof quantitative structure-activity relationships for interpretation of the migration behavior of neutral platinum (ii) complex in microemulsion electrokinetic chromatography. J. Chromatogr. A 1146,258. 

STRUCTURE-ACTIVITY RELATIONSHIPS OF PLATINUM-AMINE COMPLEXES... 

The previous sections have outlined the basic approaches to synthesis of antitumour active platinum complexes. This section intends to give some more recent and novel examples of synthetic approaches and to discuss complexes synthesized within the standard structure—activity relationships. A possible third-generation complex should also have the property of some selectivity for tumour, or specific tissue. If we consider the second-generation stage as that of obtaining a less toxic derivative, then development of more selective agents, either by selective tumour uptake or radically different biodistribution, could enhance considerably the spectrum of tumours clinically treatable. 

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