Mar. Drugs 2014, 12(3), 1545-1568; doi:10.3390/md12031545
Article

Three New and Eleven Known Unusual C25 Steroids: Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy using Diethyl Sulphate

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Received: 11 January 2014; in revised form: 25 February 2014 / Accepted: 3 March 2014 / Published: 13 March 2014
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Three new (13) and 11 known (414) C25 steroids with an unusual bicyclo[4.4.1]A/B ring system were isolated by tracing newly produced metabolites in the EtOAc extract of an antitumor mutant AD-1-2 obtained by the diethyl sulphate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. HPLC-PDAD-UV and HPLC-ESI-MS analyses indicated that the G59 strain did not produce these metabolites and the production of 114 in the mutant AD-1-2 extract was caused by the activation of silent metabolites in the original G59 strain by DES mutagenesis. The structures of the new compounds, named antineocyclocitrinols A (1) and B (2) and 23-O-methylantineocyclocitrinol (3), including their absolute configurations were determined by various spectroscopic methods, especially the NMR and Mo2-induced CD analyses. Compounds 13 provide the first examples of the C25 bicyclo[4.4.1]A/B ring steroids with the Z-configuration of 20,22-double bond. All of 114 weakly inhibited several human cancer cell lines to varying extents. These results provided additional examples for the successful application of the chemical mutagenesis strategy using DES to discover new compounds by activating silent metabolites in fungal isolates and supported also the effectiveness and usefulness of this new strategy.
Keywords: C25 steroids; antineocyclocitrinol; 23-O-methylantineocyclocitrinol; structure determination; Mo2-induced CD; dimolybdenum tetracetate; Penicillium purpurogenum; marine-derived fungus; DES mutagenesis
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MDPI and ACS Style

Xia, M.-W.; Cui, C.-B.; Li, C.-W.; Wu, C.-J. Three New and Eleven Known Unusual C25 Steroids: Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy using Diethyl Sulphate. Mar. Drugs 2014, 12, 1545-1568.

AMA Style

Xia M-W, Cui C-B, Li C-W, Wu C-J. Three New and Eleven Known Unusual C25 Steroids: Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy using Diethyl Sulphate. Marine Drugs. 2014; 12(3):1545-1568.

Chicago/Turabian Style

Xia, Ming-Wen; Cui, Cheng-Bin; Li, Chang-Wei; Wu, Chang-Jing. 2014. "Three New and Eleven Known Unusual C25 Steroids: Activated Production of Silent Metabolites in a Marine-Derived Fungus by Chemical Mutagenesis Strategy using Diethyl Sulphate." Mar. Drugs 12, no. 3: 1545-1568.

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