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DOI: 10.1055/s-0033-1348651
Calmodulin Inhibitors from the Endophytic Fungus Sporormiella minimoides
An extract of the solid cultured of Sporormiella minimoides (Sporormiaceae), isolated as endophytic fungus from Hintonia latiflora (Rubiaceae), yielded 4,9-dimethoxy-7-methyl-1H,6 H-benzo[de]isochromene-1,6-dione (1), 4-hydroxy-3,6,9-trimethoxy-7-methyl-1H,3H-benzo[de]isochromen-1-one (2), 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone (3), corymbiferone (4), ziganein (5) and brocaenol B (6). The structures of the isolates were established by spectrometric and spectroscopic methods, in particular HR-NMR techniques. Compounds 3, 5 and 6 are new natural products. All isolates were tested as potential calmodulin (CaM) inhibitors using the hCaM M124C-mBBr fluorescent biosensor but only 3 quenched significantly the extrinsic fluorescence of hCaM M124C-mBBr biosensor, with a dissociation constant (K d) value of 2.0 µM. Refined docking analysis predicted that 3 bound to CaM at site IV displaying hydrophobic interactions with Phe19, Met51, Ile52, Ile63, Phe68, Met71 y Met72 residues.