Leporizines A-C: epithiodiketopiperazines isolated from an Aspergillus species.
Three new compounds named leporizines A-C have been isolated from an Aspergillus sp. strain. Their structures were elucidated by analysis of 1D and 2D NMR spectra. Leporizines A and B were isolated during dereplication of hits from a high-throughput screening campaign for correctors of the cystic fibrosis transmembrane conductance regulator (CFTR), and leporizine C was isolated while preparing additional material for characterization of leporizines A and B. CFTR activity observed for leporizines A and B was highly correlated with cell toxicity and was determined to be a nonspecific effect. Leporizine C was not cytotoxic to cells and did not elicit a response in the CFTR assays. To the best of our knowledge, leporizines A-C represent the first examples of this unusual epithiodiketopiperazine skeleton.
AMRI, Bothell Research Center, 22215 26th Avenue SE, Bothell, Washington 98021, United States.
Ricardo
R
Reategui
Joshua
J
Rhea
Janet
J
Adolphson
Kathryn
K
Waikins
Ryan
R
Newell
John
J
Rabenstein
Ulla
U
Mocek
Michele
M
Luche
Grant
G
Carr
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001230:Aspergillus / Q000737:chemistry*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects; D054659:Diketopiperazines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D009009:Montana; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D020545:Respiratory Mucosa
D000970:Antineoplastic Agents; D054659:Diketopiperazines; C584714:leporizine A; C584715:leporizine B; C584716:leporizine C; D019005:Cystic Fibrosis Transmembrane Conductance Regulator