DNA-cleaving antitumor agents

Abstract

A chemical composition and method of use of the composition is described. The chemical composition includes an aza-enediyne, aza-enyne allene, or an aza-diallene. These compound are preferably non-hydrolyzable, cationic compounds that bind to nucleic acids. In addition it is believed that these compounds may undergo chemical reactions in the presence of a nucleic acid to generate reactive intermediates that cleave nucleic acids.

Description

Background of the invention [0001] 1. field of invention [0002] The present invention generally relates to methods and compounds for treating cancer. Specifically, one embodiment involves the use of DNA-reactive compounds that, in the presence of DNA, bind to DNA and undergo a series of chemical reactions resulting in reactive intermediates that cleave the DNA. [0003] 2. A brief description of related technologies [0004] In 1972, Robert Bergman and his collaborators proved that substituted 3-hexene-1,5-diynes (1A / 1B, figure 1 ) and proposed an intermediate 1,4-didehydrobenzene 2 in the process (Jones and Bergman, 1972). The existence of a singlet 1,4-didehydrobenzene intermediate leading to the substituted benzene product 3 was indirectly demonstrated by liquid phase CIDNP experiments (Lockhart and Bergman, 1981). Bergman's initial discovery had significant implications for the discovery of an entire class of antitumor antibiotics, beginning with calicheamicin gamm...

AI Technical Summary

Problems solved by technology

[0008] Aside from the synthetic and biological promise of enediyne and enylyne propadiene, heteroatom substitutions of these systems have not been extensively explored

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