title: Total synthesis and absolute stereochemistry of the proteasome inhibitors cystargolides A and B.
abstract: The absolute stereochemistry of the cystargolides was determined by total synthesis. Evaluation of synthetic cystargolides and derivatives showed that the natural (2S,3R) stereochemistry is essential for activity. Moreover, benzyl esters (-)-10 and (-)-15 were found to be about 100 times more potent, and to selectively kill MCF-7 cancerous cells.
authors.affiliation: Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, NM 87801, USA. rtello_a@nmt.edu.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Tello-Aburto
authors.forename: Liam P
authors.initials: LP
authors.lastname: Hallada
authors.forename: Doleshwar
authors.initials: D
authors.lastname: Niroula
authors.forename: Snezna
authors.initials: S
authors.lastname: Rogelj
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D061986:MCF-7 Cells; D008968:Molecular Conformation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004151:Dipeptides; D061988:Proteasome Inhibitors; C000600874:cystargolide A; C000600875:cystargolide B; D046988:Proteasome Endopeptidase Complex