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Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
ISSN (Print): 1871-5206
ISSN (Online): 1875-5992
Epub Full Text Article
DOI: 10.2174/18715206113136660361      Price:  $95









The Potential of Acridine Carboxamide Pt Complexes as Anti-Cancer Agents: A Review

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Author(s): Vincent Murray, Jon K. Chen and Anne M. Galea
Abstract:
There has been a concerted attempt to produce more effective anti-tumour agents based on the widely-used cancer chemotherapeutic agent, cisplatin. One interesting approach is to attach a DNA-affinic chemical group to the cisplatin molecule. This could result in a more efficient binding to the biological target, DNA, and produce a different spectrum of Pt-DNA crosslinks that may permit an agent to overcome cisplatin resistance. Acridine Pt complexes, have activity against cisplatin-resistant cells, have a differing DNA sequence selectivity compared to cisplatin and hence, are strong candidates for development as anti-tumour agents. The properties of acridine Pt analogues, especially 9-aminoacridine carboxamide Pt complexes, are reviewed here and the sequence specific interaction of acridine carboxamide Pt complexes with DNA is explored. The 9-aminoacridine carboxamide Pt complexes have a reduced reaction at runs of consecutive guanine nucleotides compared with cisplatin, and form adducts at novel DNA sequences, especially 5'-CGA. The activity of the 9-aminoacridine Pt complexes against cisplatin-resistant cell lines is due to their ability to escape the DNA repair capacity of the cells, through the production of variant DNA adducts. The future prospects for development of acridine carboxamide Pt complexes as cancer chemotherapeutic agents are discussed
Keywords:
Aminoacridine, anti-tumour agents, biological activity, cisplatin analogues, DNA-targeting, polymerase stop assay, sequence specificity
Affiliation:
School of Biotechnology and Biomolecular Sciences,University of New South Wales,Sydney, NSW 2052, Australia