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NALDC Record Details:
Absolute configuration of acremoxanthone C, a potent calmodulin inhibitor from Purpureocillium lilacinum
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Bioassay-guided fractionation of an extract prepared from the culture medium and mycelium of Purpureocillium lilacinum allowed the isolation of two calmodulin(CaM) inhibitors, namely, acremoxanthone C (1) and acremonidin A (2). The absolute configuration of 1 was established as 2R, 3R, 1′S, 11′S, and 14′R through extensive NMR spectroscopy and molecular modeling calculations at the DFT B3LYP/DGDZVP level, which included the comparison between theoretical and experimental specific rotation, 3JC,H,and 3JH,H values. Compounds 1 and 2 bind to the human calmodulin (hCaM) biosensor hCaM M124C-mBBr, with dissociation constants (Kd) of 18.25 and 19.40 nM, respectively, 70-fold higher than that of chlorpromazine (Kd = 1.24 μM), used as positive control. Docking analysis using AutoDock 4.2 predicted that 1 and 2 bind to CaM at a similar site to that which KAR-2 binds, which is unusual. Furthermore, a novel, sensible, and specific fluorescent biosensor of hCaM, i.e., hCaM T110C-mBBr, was constructed; this device is labeled at a site where classical inhibitors do not interact and was successfully applied to measure the interaction of 1 with CaM. This is the first report of xanthone−anthraquinone heterodimers in species of Paecilomyces or Purpureocillium genera.
María del Carmen González
Anthony E. Glenn
Carlos M. Cerda-García-Rojas
USDA Scientist Submission
Journal of Natural Products 2013 v.76
American Chemical Society and American Society of Pharmacognosy
Journal Articles, USDA Authors, Peer-Reviewed
Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted.
Agricultural Research Service
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