Synthesis and evaluation of a bis-3-chloropiperidine derivative incorporating an anthraquinone pharmacophore. Issue 20 (15th October 2015)

• Record Type: Journal Article
• Authors: Zuravka, Ivonne; Sosic, Alice; Gatto, Barbara; Göttlich, Richard
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 20(2015)
• Page Start: 4606
• Page End: 4609
• Publication Date: 2015-10-15
• Subjects: Alkylating agents -- Nitrogen mustard -- Anthraquinone -- DNA cleavage -- Intercalation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.08.042
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: With the aim to attain an alkylating agent with enhanced DNA-affinity, we have successfully synthesised lysine-linked bis-3-chloropiperidine1 bearing an anthraquinone moiety known to bind double-stranded DNA. Consistent with our expectations, compound1 appears to intercalate into the DNA double helix, which can be observed by conformational changes of plasmid DNA suggesting alkylation and intercalation-induced DNA unwinding. The results of this work can provide a meaningful starting point for investigating the molecular mechanism of action of this novel DNA alkylating conjugate1 with improved affinity for DNA.