Synthesis, analysis and biological evaluation of novel indolquinonecryptolepine analogues as potential anti-tumour agents. Issue 11 (19th February 2016)

• Record Type: Journal Article
• Authors: Le Gresley, A.; Gudivaka, V.; Carrington, S.; Sinclair, A.; Brown, J. E.
• Is Part Of: Organic & biomolecular chemistry. Volume 14:Issue 11(2016)
• Page Start: 3069
• Page End: 3079
• Publication Date: 2016-02-19
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob02408k
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar–phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Abstract : A small library of cryptolepine analogues were synthesised incorporating halogens and/or nitrogen containing side chains to optimise their interaction with the sugar–phosphate backbone of DNA to give improved binding, interfering with topoisomerase II hence enhancing cytotoxicity. Cell viability, DNA binding and Topoisomerase II inhibition is discussed for these compounds. Fluorescence microscopy was used to investigate the uptake of the synthesised cryptolepines into the nucleus. We report the synthesis and anti-cancer biological evaluation of nine novel cryptolepine analogues, which have greater cytotoxicity than the parent compound and are important lead compounds in the development of novel potent and selective indoloquinone anti-neoplastic agents.