DNA intercalators in cancer therapy: organic and inorganic drugs and their spectroscopic tools of analysis.
Since the discovery of the DNA intercalation process by Lerman in 1961 thousands of organic, inorganic octahedral (particularly ruthenium(II) and rhodium(III)) and square-planar (particularly platinum(II)) compounds have been developed as potential anticancer agents and diagnostic agents. The design and synthesis of new drugs is focused on bis-intercalators which have two intercalating groups linked via a variety of ligands, and synergistic drugs, which combine the anticancer properties of intercalation with other functionalities, such as covalent binding or boron-cages (for radiation therapy). Advances in spectroscopic techniques mean that the process of DNA intercalation can be examined in far greater detail than ever before, yielding important information on structure-activity relationships. In this review we examine the history and development of DNA intercalators as anticancer agents and advances in the analysis of DNA-drug interactions.
Wheate
Nial J
NJ
School of Biomedical and Health Sciences, University of Western Sydney, Penrith South DC, NSW, Australia. j.aldrich-wright@uws.edu.au
Brodie
Craig R
CR
Collins
J Grant
JG
Kemp
Sharon
S
Aldrich-Wright
Janice R
JR
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002942:Circular Dichroism; D004357:Drug Synergism; D006801:Humans; D007364:Intercalating Agents / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D011489:Protein Denaturation; D013050:Spectrometry, Fluorescence; D013057:Spectrum Analysis; D014961:X-Ray Diffraction
D000970:Antineoplastic Agents; D007364:Intercalating Agents; D009942:Organometallic Compounds