title: Synthesis and evaluation of ether-linked demethylepipodophyllotoxin dimers.
abstract: A series of novel ether-linked dimers of demethylepipodophyllotoxin are topoisomerase II poisons that exhibit higher levels of double-stranded versus single-stranded DNA cleavage than their corresponding monomers. The dimers also have higher levels of tumor cell cytotoxicity than the monomers, lending support to the two-drug model for interaction of demethylepipodophyllotoxins with human topoisomerase IIα.
authors.affiliation: Department of Chemistry, Middle Tennessee State University, 1301 Main St., Murfreesboro, TN, USA.
authors.forename: Norma
authors.initials: N
authors.lastname: Dunlap
authors.affiliation: Department of Chemistry, Middle Tennessee State University, 1301 Main St., Murfreesboro, TN, USA.
authors.forename: Tracy L J
authors.initials: TLJ
authors.lastname: Salyard
authors.affiliation: Department of Chemistry, Middle Tennessee State University, 1301 Main St., Murfreesboro, TN, USA.
authors.forename: Anuradha Liyana
authors.initials: AL
authors.lastname: Pathiranage
authors.affiliation: Department of Chemistry, Middle Tennessee State University, 1301 Main St., Murfreesboro, TN, USA.
authors.forename: Jeannie
authors.initials: J
authors.lastname: Stubblefield
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Pitts
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Ashley
authors.affiliation: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Osheroff
mesh_terms: D000951:Antigens, Neoplasm / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D004986:Ether / Q000737:chemistry*; D006801:Humans; D011034:Podophyllotoxin / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000951:Antigens, Neoplasm; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D004986:Ether; D004247:DNA; D004250:DNA Topoisomerases, Type II; D011034:Podophyllotoxin
keywords: Cytotoxicity; Demethylepipodophyllotoxin; Topoisomerase