Anthracycline and anthraquinone anticancer agents: Current status and recent developments

doi:10.1016/0163-7258(93)90006-Y

Pharmacology & Therapeutics

Volume 60, Issue 2, 1993, Pages 185-214

https://doi.org/10.1016/0163-7258(93)90006-Y Get rights and content

Abstract

The clinical treatment of neoplastic diseases relies on the complementary procedures of surgery, radiation treatment, immunotherapy and chemotherapy. The latter technique has matured from its earliest applications of mustard alkylating agents in the 1940s to an increasingly rationally based discipline, which is contributing significantly to the management of human malignancies. As the field of chemotherapy matured, several promising natural anticancer agents were identified.

However, a more urgent need soon arose from the common experience of clinically limiting toxicities of most anticancer drugs, i.e. the necessity to develop less toxic clinical drug candidates. Thus, the medicinal chemist turned towards analog development involving certain anthraquinones. Hand-in-hand with this considerable synthetic effort, which uncovered several promising clinical leads, biochemical pharmacology, or study of the mechanisms of action of clinical anticancer agents, afforded deeper insight into drug metabolism and mode of action. More recently, therefore, the field of synthetic organic chemistry, which has been complemented by the methods of microbial chemistry, has been faced with new synthetic challenges, occasioned by the identification of hitherto unrecognized cellular targets for anticancer drugs, such as topoisomerases and helicases.

The armementarium of the oncologist currently includes about 40–50 clinically useful chemical agents. The paradigm of cytotoxic anticancer agents is doxorubicin, an anthracyclin, which is still amongst the most widely prescribed and effective of anticancer agents. The review attempts to summarize the discovery of anthracyclines and the elucidation of their several mechanisms of action and efforts towards improvement of their therapeutic efficacy.

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Anthracycline and anthraquinone anticancer agents: Current status and recent developments

Abstract

Eur. J. Cancer

Carbohydrate Res.

Tetrahedron Lett.

N-Alkylation of anthracyclines

Morpholinyl anthracyclines

Synthesis of new doxorubicin analogs

Daunomycin I the structure of daunomycin

J. Am. Chem. Soc.

Conversion of daunomycin to adriamycin

Chim. Ind. (Milan)

Adriamycin, 14-hydroxydaunomycin, a new antitumor antibiotic from S. peucetius var. caesius

Biotechnol. Bioeng.

Adriamycin (14-hydroxydaunomycin) a novel antitumor antibiotic

Tetrahedron Lett.

Synthesis and biological evaluation of some 14-O-acyl derivatives of adriamycin

J. Med. Chem.

Adriamycin (NSC-123127): new chemical developments and analogs

Cancer Chemother. Rep.

Synthesis and antitumor activity of 4-demethoxydaunorubicin, 4-demethoxy-7,9-diepidaunorubicin and their β-anomers

Cancer Treat. Rep.

Daunomycin derivatives

Doxorubicin thioester

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J. Antibiot. (Tokyo)

Daunorubicinol, a major metabolite of daunorubicin: isolation from human urine and enzymatic reactions

J. Pharmac. exp. Ther.

Daunorubicin metabolism by rat tissue preparations

J. Pharmac. exp. Ther.

Helicase inhibition by anthracycline anticancer agents

Molec. Pharmac.

Iron(III) adriamycin and iron(III)-daunorubicin complexes. Physicochemical characteristics, interaction with DNA and antitumor activity

Biochemistry

Anthracycline derivatives

Cardiac toxicity of daunomycin

Lancet

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Antibiotiki (Moscow)

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Naturewissenschaften

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Chem. Ber.

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Chem. Ber.

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Naturwissenschaftern

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Un novel antibiotique a proprietes cytostatiques: la rubidomycine

C. R. Acad. Sci. Paris

Daunorubicin derivatives

Molecular pharmacology of anthracyclines: demonstration of multiple mechanistic classes of anthracyclines

Stoffwechselprodukte von actinomyceten, XVI cinerubine

Chem. Ber.

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J. Antibiot. (Tokyo)

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Cancer Res.

Metal anthracyclines and anthracenedione complexes, a new class of anticancer agents

Cinchonine, a potent efflux inhibitor to circumvent anthracycline resistance in vivo

Cancer Res.

4-Demethoxy-9-deoxy-9-methyldaunorubicin

Gazz. Chim. Ital.

A differential interaction of daunomycin, adriamycin and their derivatives with human erythrocytes and phospholipid bilayers

Biochim. biophys. Acta

Synthesis of daunorubicin-14 ¹⁴C and adriamycin-14 ¹⁴C