ChemInform Abstract: STRUCTURE OF THE DNA COMPLEXING AGENT ANTHRAMYCIN

Mostad, Arvid; Roemming, C.; STORM, B.

doi:10.1002/chin.197914064

Chemischer Informationsdienst

1979

DOI: 10.1002/chin.197914064

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ChemInform Abstract: STRUCTURE OF THE DNA COMPLEXING AGENT ANTHRAMYCIN

Arvid Mostad¹,

C. Roemming²,

B. STORM³

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1981

1984

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Hurley¹,

Thurston²

1984

Pharmaceutical Research

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The pyrrolo(l,4)benzodiazepine (P(1,4)B) antitumor antibiotics, anthramycin, tomaymycin, sibiromycin and the neothramycins A and B, are potent anticancer agents that form covalent adducts through the exocyclic amino group of guanine in DNA. This review describes the chemistry important for both the DNA reactivity and synthesis of the carbinolamine containing drugs and the strategy for elucidation of the three-dimensional form of the adduct with DNA. The high DNA sequence specificity as well as some of the observed biological consequences of DNA damage caused by these agents in human and yeast cells are rationalized through the proposed structure of the drug-DNA adducts. Parallel toxicological studies have led to a proposal for the underlying mechanism for the cardiotoxicity of certain members of this group of agents. A rationale for designing drugs which should retain their potent antitumor activity without the associated cardiotoxicity is also proposed. Lastly, the application of the P(l,4)B's as probes for monitoring drug binding to DNA and drug-induced conformational changes is described.

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Hurley¹,

Thurston²

1984

Pharmaceutical Research

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Structure of tomaymycin, a DNA binding antitumor antibiotic.

Arora¹

1981

J. Antibiot.

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ChemInform Abstract: STRUCTURE OF THE DNA COMPLEXING AGENT ANTHRAMYCIN

Cited by 2 publications

References 1 publication

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Untitled

Structure of tomaymycin, a DNA binding antitumor antibiotic.

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