Doxorubicin molecular structure

Antibiotic C-1027 (61) was isolated from the cultivation broth of S. globisporus [59] and its molecular weight was determined to be 15 000 [60]. The chromophore part of this antibiotic [60] contains a 9-membered ring incorporated into the 16-membered macrocycle [61]. Complexity of its structure was described several times [61,62] and its absolute stereochemistry was determined on the basis of not only 2D NMR but also of CD spectra. Its high cytotoxicity exceeds even that of doxorubicin [63]. S. graminofaciens was several times erratically described [64,65], as a producer of chlorinated flavone derivatives (62,63). 

Figure 7.6. Drugs that are structural analogs of riboflavin and may cause deficiency. Relative molecular masses (Mr) riboflavin, 376.4 quinacrine, 472.9 (dihydrochloride) chlorpromazine, 318.9 imipramine, 280.4 amitryptyline, 277.4 and adriamycin (doxorubicin), 543.5.

A considerable amount of research has gone into elucidating the molecular mechanism of action of these antitumour quinones. While several mechanisms are possible, a single mechanism may not fully explain all of the observed cytotoxic effects. One of the objectives of the NCI and other studies elsewhere has been to determine if there were any structure-activity relationships within the major structural groups ranging from the simplest benzoquinones to the complex multiple heteroatom quinones. One of the main conclusions from these studies was that the most active compounds were mitomycin C, the 3,6-diaziridinylbenzoquinones with 2,5-alkylamino substituents, adriamycin (doxorubicin), daunomycin (daunorubicin) and AZQ (Figure 1). 

Fig. 2 Structure of W-(2-hydroxypropyl) methacrylamide copolymer incorporating doxorubicin (PK-1), the first polymer-drug conjugate to reach clinical trials. The molecular weight of the polymer-drug conjugate is 28 kDa and the drug content is 8.5% (w/w) [16]...

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