Truncated azinomycin analogues intercalate into DNA

• Published in: Bioorganic & medicinal chemistry letters Vol. 15; no. 3; pp. 653 - 656
• Main Authors: Casely-Hayford, Maxwell A., Pors, Klaus, Patterson, Laurence H., Gerner, Clive, Neidle, Stephen, Searcey, Mark
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.02.2005; Elsevier
• Subjects: Analogues; Antibiotics, Antineoplastic - chemical synthesis; Antibiotics, Antineoplastic - pharmacology; Antineoplastic agents; Azabicyclo Compounds; Azinomycin; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; Dipeptides; DNA - chemistry; DNA - drug effects; DNA - metabolism; DNA unwinding; General aspects; Glycopeptides - chemical synthesis; Glycopeptides - chemistry; Humans; Intercalating Agents - chemical synthesis; Intercalation; Medical sciences; Nucleic Acid Denaturation - drug effects; Pharmacology. Drug treatments; Piperidines - chemistry; Structure-Activity Relationship; Synthesis; Synthesis; Intercalation; Analogues; DNA unwinding; Azinomycin; Antineoplastic agent; Intercalating agent; DNA; Piperidine derivatives; Binding mode; Oxirane derivatives; Carboxamide; Chemical synthesis; Naphthalene derivatives; Biological activity; Duplex
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2004.11.037

A designed analogue of the left half of azinomycin has been synthesized and unwinds supercoiled DNA. The design and synthesis of a potentially more therapeutically-viable azinomycin analogue 4 based upon 3 has been completed. It involved coupling of a piperidine mustard to the acid chloride of the azinomycin chromophore. Both the designed azinomycin analogue 4 and the natural product 3 bind to DNA and cause unwinding, supporting an intercalative mode of binding.