ABSTRACT
@#Platinum antitumor drugs are widely used for clinical treatment because of their unique antitumor mechanisms, significant antitumor effects, and broad antitumor spectrum. Yet shortcomings such as toxic side effects, drug resistance and cross-resistance of platinum-based drugs have limited their further application. Platinum-intercalator conjugates possess different antitumor mechanisms from those of classic platinum drugs, and have unique advantages in overcoming the disadvantages of classic platinum antitumor drugs. The platinum-intercalator conjugates can be classified into six categories based on the different DNA-intercalator: platinum-acridine, platinum-quinoline, platinum-indole, platinum-naphthalimides, platinum-anthraquinone and platinum-based antitumor agents containing other types of intercalating groups. This article summarizes the research progress of platinum-based antitumor drugs containing DNA insertion groups in recent years.
ABSTRACT
One class of small molecules with therapeutic potential for treatment of cancer functions as transcription inhibitors via interaction with double-stranded DNA. Majority of the studies of the interaction with DNA have so far been reported under conditions nonexistent in vivo. Inside the cell, DNA is present in the nucleus as a complex with proteins known as chromatin. For the last few years we have been studying the interaction of these DNA-binding small molecules at the chromatin level with emphasis on the drug-induced structural alterations in chromatin. Our studies have shown that at the chromatin level these molecules could be classified in two broad categories: single-binding and dual-binding molecules. Single-binding molecules access only DNA in the chromatin, while the dual-binding molecules could bind to both DNA and the associated histone(s). Structural effects of the DNA-binding molecules upon chromatin in light of the above broad categories and the associated biological implications of the two types of binding are discussed.