title: Structure-activity relationships of epolactaene derivatives: structural requirements for inhibition of Hsp60 chaperone activity.
abstract: Epolactaene is a microbial metabolite isolated from the fungal strain Penicillium sp. It arrests the cell cycle at the G0/G1 phase and induces the outgrowth of neurites in human neuroblastoma SH-SY5Y cells. In this communication, we report the structure-activity relationships (SARs) of new epolactaene derivatives, including those lacking the epoxylactam moiety and having various side chains. These derivatives were evaluated for their ability to inhibit the growth of human cancer cell lines. They were also analyzed for their ability to affect human heat shock protein 60 (Hsp60), which we have already identified as a protein that binds to epolactaene. We also identified the important structural framework of epolactaene/ETB (epolactaene tertiary butyl ester) for not only binding to Hsp60 but also inhibiting Hsp60 chaperone activity.
authors.affiliation: Antibiotics Laboratory, RIKEN Discovery Research Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Nagumo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kakeya
authors.forename: Junichiro
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Takao
authors.initials: T
authors.lastname: Uno
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Shoji
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Osada
mesh_terms: D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D018834:Chaperonin 60 / Q000378:metabolism*; D004852:Epoxy Compounds / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D011090:Polyenes / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship
chemical_list: D018834:Chaperonin 60; D004852:Epoxy Compounds; D011090:Polyenes; C095351:epolactaene