Isolation and characterization of two verrucarins from Myrothecium roridum.
In the course of a screening for compounds inhibiting the growth of two human breast cancer cells lines, two highly cytotoxic compounds were isolated from fermentations of Myrothecium roridum. The elucidation of their structures revealed that they are macrocyclic trichothecenes of the verrucarin type, 16-hydroxyverrucarin A (1), reported here as a natural product for the first time, and verrucarin X (2), a new compound. Both 1 and 2 exhibit moderate antifungal activity and pronounced cytotoxic activity, with IC50 values in the nanomolar (1) and micromolar (2) range. Both compounds preferentially inhibit in vivo protein biosynthesis.
Schoettler
Sylvia
S
Department of Biotechnology, University of Kaiserslautern, Paul-Ehrlich-Str. 23, D-67663 Kaiserslautern, Germany.
Bascope
Marcelo
M
Sterner
Olov
O
Anke
Timm
T
D000230:Adenocarcinoma; D001203:Ascomycota; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014255:Trichothecenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
D018942:Macrolides; D011500:Protein Synthesis Inhibitors; D014255:Trichothecenes; C513952:verrucarin X; C513953:16-hydroxyverrucarin A; C005348:muconomycin A