Dereplication of macrocyclic trichothecenes from extracts of filamentous fungi through UV and NMR profiles.
Macrocyclic trichothecenes (MTs), which have potent cytotoxicity, have been isolated from many different fungal species. These compounds were evaluated clinically by the US National Cancer Institute in the 1970s and 1980s. However, they have yet to be advanced into viable drugs because of severe side effects. Our team is investigating a diverse library of filamentous fungi for new anticancer leads. To avoid reisolating MTs through bioactivity-directed fractionation studies, a protocol for their facile dereplication was developed. The method uses readily available photodiode array detectors to identify one of two types of characteristic UV spectra for these compounds. In addition, diagnostic signals can be observed in the (1)H-NMR spectra, particularly for the epoxide and conjugated diene moieties, even at the level of a crude extract. Using these techniques in a complementary manner, MTs can be dereplicated rapidly.
Sy-Cordero
Arlene A
AA
Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC 27402, USA.
Graf
Tyler N
TN
Wani
Mansukh C
MC
Kroll
David J
DJ
Pearce
Cedric J
CJ
Oberlies
Nicholas H
NH
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification*; D045744:Cell Line, Tumor; D005658:Fungi / Q000737:chemistry; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet; D014255:Trichothecenes / Q000737:chemistry* / Q000302:isolation & purification*
D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D014255:Trichothecenes