title: Antitumor agents. Part 227: Studies on novel 4'-O-demethyl-epipodophyllotoxins as antitumor agents targeting topoisomerase II.
abstract: Eight novel epipodophyllotoxin derivatives (6-13), which were designed to overcome drug resistance and enhance topoisomerase II inhibition, were synthesized and evaluated. Two of these compounds (7 and 8) showed better preclinical activity profiles, including cell growth inhibition, cell killing, and in vitro topoisomerase II inhibition, as compared to the prototype molecule etoposide (1). They also retained the superior drug-resistance profile of GL-331 (4), an epipodophyllotoxin derivative currently in clinical evaluation.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Xiao
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: John R
authors.initials: JR
authors.lastname: Vance
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006801:Humans; D015394:Molecular Structure; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D059005:Topoisomerase II Inhibitors; D004247:DNA; D004250:DNA Topoisomerases, Type II; D011034:Podophyllotoxin; C072088:4'-demethylepipodophyllotoxin