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ID: ALA1137028

Journal: Bioorg Med Chem Lett

Title: Structure-activity relationships of epolactaene derivatives: structural requirements for inhibition of Hsp60 chaperone activity.

Authors: Nagumo Y, Kakeya H, Yamaguchi J, Uno T, Shoji M, Hayashi Y, Osada H.

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.

CiteXplore: 15357965

DOI: 10.1016/j.bmcl.2004.06.054