Synthesis of7-Amino-6-Methoxy-5,8-Quinolinequinone Derivatives

Abstract

Streptonigrin, a derivative of 7-amino-6-methoxy-5,8-quinolinequinone, was first isolated from the bacterium Streptomyces flocculus forty years ago. It has proven to be a good substrate of NAD(P)H: quinone oxidoreductase, which is over expressed in tumors of the colon, breasts and lungs. It is suggested that the enzymatic process of NAD(P)H: quinone oxidoreductase with streptonigrin produces hydroxy (OH) radical that induces the breakage of DNA strands and consequently, various cell toxins. Recently, a less complicated family of streptonigrin has proven to be a more effective substrate for the NAD(P)H: quinone oxidoreductase. The simplest member of this family, 6-methoxy-5,8-quinolinequinone, is prepared via a four-step synthesis starting from the commercially available 6-hydroxyquinoline. Thus far, we have synthesized 6-methoxy-5,8-quinolinequinone and have attempted to derive a structure that better resembles streptonigrin. For example, we introduced various N substituents at the compound?s 7th position. We expect this new family to be a better substrate for NAD(P)H: quinone oxidoreductase, thus functioning as a more effective antitumor agent.