Dynemicin A is a potent antibacterial and antitumor antibiotic having a striking hybrid structure combining the characteristics of both the anthraquinone as a DNA intercalator and diynene as a DNA strand breaker. We investigated the DNA-binding properties of five non-diynene dynemicins and of several related tri-and pentacyclic aza-anthraquinones (1-4). Pentacyclic quinones 1 and 2 were synthesized as shown in Scheme 4. The key step was photochemical cyclization of 11 that proceeded smoothly to afford 17 and 18 with no diastereoselectivity (Scheme 2). Tricyclicquinone 3 was prepared according to the reported procedure (Scheme 5). Since O-methylation of 3 was unsuccessful, tricyclicquinone 4 was synthesized as shown in Scheme 6. Addition of excess DNA to a drug solution induced a pronounced red shifts in UV absorption spectrum of the drug. All dynemicins examined showed similar binding ability with DNA (Figure 3). As expected, a binding of the synthetic anthraquinones with DNA varied depend on their structure. Since supercoiled DNA incubated with these non-diynene dynemicins was retarded on electrophoresis (Figure 4), intercalative binding of these drugs to DNA is suggested. On the other hand, the synthetic anthraquinones 1-4 had no effect on the electrophoretic mobility, suggesting that the gross structure of supercoiled DNA is not changed by the binding of these drugs. This is surprising since the non-diynene dynemicins are presumed to bind intercalatively to DNA through the aza-anthraquinone moiety. In order to investigate the function of this partial structure in dynemicins in their intercalation with DNA, synthesis of anthraquinones more closely related to the dynemicin substructure is currently in progress.
