Targeting radiosensitizers to DNA by minor groove binding: nitroarenes based on netropsin and distamycin

Four analogues of the antitumour antibiotics, netropsin and distamycin, containing 2-nitroimidazole or 5-nitrofuran moieties were synthesised. All showed high affinity for DNA, including compounds with only one pyrrole/amidine moiety, but the radiosensitizing efficiencies were poor. The results have...

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Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 3; no. 8; pp. 1697 - 1702
Main Authors Parrick, John, Porssa, Manuchehr, Davies, Lisa K., Dennis, Madeleine F., Patel, Kantilal B., Stratford, Michael R.L., Wardman, Peter
Format Journal Article
LanguageEnglish
Published Oxford Elsevier Ltd 01.08.1993
Elsevier
Subjects
Antineoplastic agents
Biological and medical sciences
General aspects
Medical sciences
Pharmacology. Drug treatments
Antineoplastic agent
Antibiotic
Radiosensitizing agent
Synthesis
Structure activity relation
Molecular structure
DNA
Affinity
Drug targeting
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Summary:Four analogues of the antitumour antibiotics, netropsin and distamycin, containing 2-nitroimidazole or 5-nitrofuran moieties were synthesised. All showed high affinity for DNA, including compounds with only one pyrrole/amidine moiety, but the radiosensitizing efficiencies were poor. The results have implications both for minor groove targeting and the design of radiosensitizers. The compounds bind strongly to DNA, even when n = 1. This finding is of relevance to other chemotherapeutic agents acting on DNA, even though radiosensitization is not enhanced by targeting in this way.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(00)80045-1