title: Synthesis and evaluation of the apoptosis inducing and CT DNA interaction properties of a series of 4β-carbamoyl 4'-O-demethylepipodophyllotoxins.
abstract: A series of carbamate derivatives of 4'-demethylepipodophyllotoxin have been synthesized, and their cytotoxicities against several human cancer cell lines, including HeLa, A549, HCT-8, and HL-60 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-4'-Demethylepipodophyllotoxin 1-(4-nitrophenyl) piperazinyl carbamate (19) was found to be the most potent compound of those synthesized in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of Bax, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.
authors.affiliation: School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Sang
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Liu
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Qin
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Hui
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Jin
authors.forename: Shi-Wu
authors.initials: SW
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D004247:DNA; C427203:calf thymus DNA
keywords: Apoptosis; CT DNA; Carbamates; Cytotoxicity; Podophyllotoxin