title: Fluorescent 7-diethylaminocoumarin pyrrolobenzodiazepine conjugates: synthesis, DNA interaction, cytotoxicity and differential cellular localization.
abstract: The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a class of DNA minor groove binding agents that react covalently with guanine bases, preferably at Pu-G-Pu sites. A series of three fluorescent PBD-coumarin conjugates with different linker architectures has been synthesized to probe correlations between DNA binding affinity, cellular localization and cytotoxicity. The results show that the linker structure plays a critical role for all three parameters.
authors.affiliation: Cancer Research UK Gene Targeted Drug Design Research Group, School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Wells
authors.forename: Marie
authors.initials: M
authors.lastname: Suggitt
authors.forename: Marissa
authors.initials: M
authors.lastname: Coffils
authors.forename: Mirza A H
authors.initials: MA
authors.lastname: Baig
authors.forename: Philip W
authors.initials: PW
authors.lastname: Howard
authors.forename: Paul M
authors.initials: PM
authors.lastname: Loadman
authors.forename: John A
authors.initials: JA
authors.lastname: Hartley
authors.forename: Terence C
authors.initials: TC
authors.lastname: Jenkins
authors.forename: David E
authors.initials: DE
authors.lastname: Thurston
mesh_terms: D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D003593:Cytoplasm / Q000187:drug effects* / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D005260:Female; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D011758:Pyrroles; C438462:pyrrolo(2,1-c)(1,4)benzodiazepine; D001569:Benzodiazepines; D004247:DNA; C427203:calf thymus DNA