Anthracycline antibiotics antitumor activity

Anthracyclines are antitumor quinone containing antibiotics produced by different strains of Streptomyces. Some of them, such as adriamycin doxorubicin), and daunorubicin are broad spectrum antitumor compounds. They act by binding to DNA and interfering with DNA replication and gene transcription. Their limitations for clinical use are cardiac toxicity and drug resistance phenomena. Consequently, intense structure-activity relationship studies have been performed to improve the pharmacological profile as well as to enhance the affinity for DNA. In particular, a number of fluorinated anthracyclines have been prepared with introduction of fluorine atoms into D or A cycles, and into the aglycone side chain linked atC-14. ... 

Zou Y et al (1994) Antitumor activity of free and liposome-entrapped annamycin, a lipophilic anthracycline antibiotic with non-cross-resistance properties. Cancer Res 54 1479-1484... 

Interestingly, the nature of the acetal moiety appears to affect the potency of the antibiotic. For instance, baumycins containing a carbinolaminc moiety (c.g., barmino-mycins) generally exhibit a greater cytotoxicity and antitumor activity than the classical anthracyclines (38). In addition, structural variations may occur at C4 or Cl 3 of the anthracyclinone moiety, which may affect the compound s activity (34-37). 

Hori S, Shirai M. Hirano S, Oki T, Inui T, Tsukagoshi S, Ishizuka M, Takeuchi T, Umezawa H. Antitumor activity of new anthracycline antibiotics, aclacinomycin-A and its analogs, and their toxicity. Gann 1977 68 685-690. 

It is well known that anthracycline antibiotics having an anthra-quinone group in the molecule are an important class of widely used antitumor antibiotics. Their clinical efficacy is limited by severe dose-related cardiotoxicity 2 It j s been considered that these undesirable side effects as well as the clinical benefits result from their ability to shuttle electrons from NADPH-cytochrome P-450 reductase to molecular oxygen that is, in turn, transformed into activated oxygen species such as superoxide anion radical, hydroxyl radical, and hydrogen peroxide - activated oxygen species have been proposed to play a fatal role in DNA scission and peroxidation of mitochondrial membranes . However, the detailed mechanism is not yet fully understood. 

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