title: Enediyne-lexitropsin DNA-targeted anticancer agents. Physicochemical and cytotoxic properties in human neoplastic cells in vitro, and intracellular distribution.
abstract: Two series of hybrids of a dynemicin A model and DNA minor groove binding lexitropsins were synthesized and their cytotoxic activities were investigated in a panel of human normal and malignant cell lines using a colorimetric assay. Adriamycin was used as a control. Several of the agents demonstrated cytotoxic activity, the extent of which varied with tumor type. IC50s of the hybrids ranged from approximately 14-48 microM following 96 h incubation in the presence of test compound. Intracellular distribution studies were facilitated through endogenous fluorescence of the compounds. Evidence of nuclear uptake of the hybrid agents was demonstrated by confocal laser scanning microscopy. The results warrant further development of DNA-targeted enediyne-lexitropsin hybrids as potential anticancer agents.
authors.affiliation: Department of Chemistry, University of Alberta, Edmonton, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.forename: G G
authors.initials: GG
authors.lastname: Miller
authors.forename: S A
authors.initials: SA
authors.lastname: Cubitt
authors.forename: K J
authors.initials: KJ
authors.lastname: Soderlind
authors.forename: M J
authors.initials: MJ
authors.lastname: Allalunis-Turner
authors.forename: J W
authors.initials: JW
authors.lastname: Lown
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002460:Cell Line; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009429:Netropsin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; C053654:lexitropsin; D009429:Netropsin