title: Synthesis, analysis and biological evaluation of novel indolquinonecryptolepine analogues as potential anti-tumour agents.
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.
authors.affiliation: School of Life, Chemical and Pharmaceutical Sciences, SEC Faculty, Kingston University, Kingston-upon-Thames, KT1 2EE, UK. a.legresley@kingston.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Le Gresley
authors.forename: V
authors.initials: V
authors.lastname: Gudivaka
authors.forename: S
authors.initials: S
authors.lastname: Carrington
authors.forename: A
authors.initials: A
authors.lastname: Sinclair
authors.forename: J E
authors.initials: JE
authors.lastname: Brown
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045563:Indolequinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D045563:Indolequinones; D011804:Quinolines; D059005:Topoisomerase II Inhibitors; C024015:cryptolepine; D004250:DNA Topoisomerases, Type II