title: Calmodulin inhibitors from Aspergillus stromatoides.
abstract: An organic extract was prepared from the culture medium and mycelia of the marine fungus Aspergillus stromatoides RAPER & FENNELL. The extract was fractionated via column chromatography, and the resulting fractions were tested for their abilities to quench the fluorescence of the calmodulin (CaM) biosensor hCaM M124C-mBBr. From the active fraction, emodin (1) and ω-hydroxyemodin (2) were isolated as CaM inhibitors. Anthraquinones 1 and 2 quenched the fluorescence of the hCaM M124C-mBBr biosensor in a concentration-dependent manner with K(d) values of 0.33 and 0.76 μM, respectively. The results were compared with those of chlorpromazine (CPZ), a classical inhibitor of CaM, with a K(d) value of 1.25 μM. Docking analysis revealed that 1 and 2 bind to the same pocket of CPZ. The CaM inhibitor properties of 1 and 2 were correlated with some of their reported biological properties. Citrinin (3), methyl 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (4), and coniochaetone A (5) were also isolated in the present study. The X-ray structure of 5 is reported for the first time.
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, México.
authors.forename: Martín
authors.initials: M
authors.lastname: González-Andrade
authors.forename: Paulina
authors.initials: P
authors.lastname: Del Valle
authors.forename: Martha L
authors.initials: ML
authors.lastname: Macías-Rubalcava
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosa-Peinado
authors.forename: María
authors.initials: M
authors.lastname: Del Carmen González
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D001230:Aspergillus / Q000737:chemistry*; D001665:Binding Sites; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002746:Chlorpromazine / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003470:Culture Media / Q000737:chemistry; D004642:Emodin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D000880:Anthraquinones; D002147:Calmodulin; D003470:Culture Media; D004642:Emodin; D002746:Chlorpromazine