Calmodulin Inhibitors from Aspergillus stromatoides |
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| Authors: | Martín González‐Andrade,Paulina Del Valle,Martha L. Macías‐Rubalcava,Alejandro Sosa‐Peinado,María Del Carmen González,Rachel Mata |
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| Affiliation: | 1. Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, México, (phone: +525‐55‐622‐5289);2. Instituto Nacional de Medicina Genómica (INMEGEN), Secretaría de Salud, México City DF 14610, México;3. Instituto de Química, Universidad Nacional Autónoma de México, México DF 04510, México;4. Facultad de Medicina, Universidad Nacional Autónoma de México, México DF 04510, México;5. Instituto de Biología, Universidad Nacional Autónoma de México, México DF 04510, México |
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| 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 Kd 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 Kd 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. |
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| Keywords: | Aspergillus stromatoides Emodin Fungi Calmodulin Inhibitors Marine fungi X‐Ray crystallography |
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