title: Synthesis and evaluation of novel caged DNA alkylating agents bearing 3,4-epoxypiperidine structure.
abstract: Previously, we reported that the 3,4-epoxypiperidine structure, whose design was based on the active site of DNA alkylating antitumor antibiotics, azinomycins A and B, possesses prominent DNA cleavage activity. In this report, novel caged DNA alkylating agents, which were designed to be activated by UV irradiation, were synthesized by the introduction of four photo-labile protecting groups to a 3,4-epoxypiperidine derivative. The DNA cleavage activity and cytotoxicity of the caged DNA alkylating agents were examined under UV irradiation. Four caged DNA alkylating agents showed various degrees of bioactivity depending on the photosensitivity of the protecting groups.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kodama
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Miyashita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imanishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Obika
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: C465229:3,4-epoxypiperidine; D018906:Antineoplastic Agents, Alkylating; D004852:Epoxy Compounds; D010880:Piperidines; D004247:DNA