Macromolecular antiproliferative agents featuring dicarboxylato-chelated platinum

Show simple item record Komane, L.L. Mukaya, E.H. Neuse, E.W. Jansen van Rensburg, Connie E. 2009-03-30T10:26:25Z 2009-03-30T10:26:25Z 2008
dc.description.abstract Cancerous diseases, together with cardiac afflictions, account for the predominant causes of death among the adult population of the Western world. The classical platinum drugs, with cisplatin as their parent, have established themselves for years as leading components in the oncologist’s arsenal of antitumor agents. As with most other antineoplastic drugs, however, incisive pharmacological deficiencies, notably excessive systemic toxicity and induction of drug resistance, have severely curtailed their overall efficaciousness. With the objective of overcoming these counterproductive deficiencies, the technique of polymer-drug conjugation, representing an advanced modality of drug delivery, has been developed in recent years to high standards worldwide. In a drug conjugate, water-soluble macromolecular carrier constructs designed in compliance with stringent pharmacological specifications are covalently, yet bioreversibly, interconnected with the bioactive agent. As a macromolecule following a pharmacokinetic pathway different from that of non-polymeric compounds, the conjugate acts as a pro-drug favorably transporting the agent through the various body compartments to, and into, the target cell, where the agent is enzymatically or hydrolytically separated from the carrier for its biological action. In the authors’ laboratories the conjugation strategy has been adopted as the primary tool for drug efficacy enhancement. The present paper describes a special type of platinum complex carrier-bound via dicarboxymetal chelation, synthesized from carboxyl-functionalized polyamide-type carriers by platination with trans-1,2-diaminocyclohexanediaquaplatinum(II) dinitrate. In a series of in vitro tests antiproliferative activities have been determined against several human cancer cell lines. Whereas no improvements are observed in tests against a colorectal cancer, outstanding findings of the screening program include a 10- to 100-fold increase in cell-killing performance of the conjugates relative to the (non-polymeric) cisplatin standard against the HeLa adenocarcinoma, and distinctly reduced resistance factors (again, relative to cisplatin) in tests against the A2780 and A2780-cis pair of ovarian cell lines. These findings augur well for future developments of this class of platinum drugs. en_US
dc.identifier.citation Komane, LL, Mukaya, EH, Neuse, EW & Van Rensburg, CEJ 2008, ‘Macromolecular antiproliferative agents featuring dicarboxylato-chelated platinum', Journal of Inorganic and Organometallic Polymers and Materials, vol. 18, no. 1, pp. 111-123 en_US
dc.identifier.issn 1574-1451
dc.identifier.other 10.1007/s10904-007-9175-7
dc.language.iso en en_US
dc.publisher Springer en_US
dc.rights Springer. The origincal publication is available at en_US
dc.subject Platinum drugs en_US
dc.subject Anticancer agents en_US
dc.subject Polymer-drug conjugates en_US
dc.subject.lcsh Cisplatin
dc.subject.lcsh Toxicology
dc.subject.lcsh Drug resistance
dc.subject.lcsh Antineoplastic agents
dc.subject.lcsh Drugs -- Research
dc.title Macromolecular antiproliferative agents featuring dicarboxylato-chelated platinum en_US
dc.type Postprint Article en_US

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