title: Biosynthetic O-methylation protects cladoniamides from self-destruction.
abstract: Bisindole cladoniamides, nanomolar inhibitors of colon cancer cell line HCT-116, contain a rare, indolotryptoline substructure. In this report, the structures of xenocladoniamides A-E (9-13) are described. Compounds 9-13 are generated from a cladoniamide heterologous production system where O-methyltransferase gene claM3 has been inactivated. The results suggest that O-methylation, installed by enzyme ClaM3, is critical to maintaining the structural integrity of the indolotryptoline scaffold. Xenocladoniamides D and E are modestly cytotoxic against colon cancer cell line HCT-116.
authors: Department of Chemistry, University of British Columbia , Vancouver, B.C. Canada.
authors: Yi-Ling
authors: YL
authors: Du
authors: Tong
authors: T
authors: Ding
authors: Katherine S
authors: KS
authors: Ryan
mesh_terms: D053898:Biosynthetic Pathways; D002243:Carbolines / Q000737:chemistry*; D045744:Cell Line, Tumor; D045325:HCT116 Cells / Q000737:chemistry*; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry* / Q000378:metabolism; D008745:Methylation; D015394:Molecular Structure
chemical_list: D002243:Carbolines; D026121:Indole Alkaloids; C581998:cladoniamide G; C009804:tryptoline