Potential antitumor agents. 44. Synthesis and antitumor activity of new classes of diacridines: importance of linker chain rigidity for DNA binding kinetics and biological …

…, GJ Atwell, BC Baguley, LPG Wakelin

Index: Denny; Atwell; Baguley; Wakelin Journal of Medicinal Chemistry, 1985 , vol. 28, # 11 p. 1568 - 1574

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Citation Number: 80

Abstract

Four classes of diacridines, joined at the 9-position by linker chains of varying length, rigidity, and polarity, were evaluated for DNA-binding properties and antitumor activity. Diacridines linked by flexible chains of varying polarity show relatively fast chromophore exchange kinetics among DNA binding sites but slower dissociation rates, suggesting the potential for considerable “creeping” of the drug along the helix, and are inactive in vivo. ...