title: Total Synthesis and Biological Studies of TMC-205 and Analogues as Anticancer Agents and Activators of SV40 Promoter.
abstract: TMC-205 is a natural fungal metabolite with antiproliferative activity against cancer cell lines. The light- and air-sensitivity prevented in-depth exploitation of this novel indole derivative. Herein, we report the first synthesis of TMC-205. On the basis of its reactivity with reactive oxygen species, we developed air-stable analogues of TMC-205. These analogues are 2-8-fold more cytotoxic than TMC-205 against HCT-116 colon cancer cell line. Importantly, at noncytotoxic dose levels, these analogues activated the transcription of luciferase reporter gene driven by simian virus 40 promoter (SV40). Further, these small molecules also inhibit firefly luciferase, presumably by direct interaction.
authors.affiliation: Department of Chemistry, University of Pittsburgh , 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Chemistry, University of Pittsburgh , 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Sami
authors.initials: S
authors.lastname: Osman
authors.affiliation: Department of Chemistry, University of Pittsburgh , 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Koide
keywords: TMC-205; firefly luciferase; gene activation; indole,; natural product; simian virus 40 promoter