The Potential of Acridine Carboxamide Pt Complexes as Anti-Cancer Agents : A Review
Vincent Murray, Jon K. Chen and Anne M. Galea
Affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
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
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