<span style="font-family:Verdana;">Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (</span><...<span style="font-family:Verdana;">Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (</span><b><span style="font-family:Verdana;">1</span></b><span style="font-family:Verdana;">) with </span><i><span style="font-family:Verdana;">Fusarium lini</span></i><span> </span><span style="font-family:Verdana;">NRRL 2204 was carried out for the first time, yielding two new metabolites, 3,7</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-dihydroxy-19-norandrost-1,3,5-trien-17-one</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">(</span><b><span style="font-family:Verdana;">3</span></b><span style="font-family:Verdana;">) and 6</span><i><span style="font-family:Verdana;">α</span></i></span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;">10</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;">17</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-trihydroxy-19-nor-4-androsten-3-one</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">(</span><b><span style="font-family:Verdana;">4</span></b><span style="font-family:Verdana;">), along</span></span><span style="font-family:Verdana;"> with three known compounds, </span><span style="font-family:""><span style="font-family:Verdana;">3</span><b><span style="font-family:Verdana;">-</span></b><span style="font-family:Verdana;">hydroxy-19-norandrost-1,3,5-trien-17-one (</span><b><span style="font-family:Verdana;">2</span></b><span style="font-family:Verdana;">), 10</span></span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:""><span style="font-family:Verdana;">,</span><i> </i></span><span style="font-family:Verdana;">17</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:""><span style="font-family:Verdana;">-dihydroxy-19-nor-4-androsten-3-one (</span><b><span style="font-family:Verdana;">5</span></b><span style="font-family:Verdana;">) and</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">10</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-hydroxy-19-nor-4-</span><span style="font-family:""> </span><span style="font-family:Verdana;">androsten-3</span><span style="font-family:Verdana;">,</span><span style="font-family:""><span style="font-family:Verdana;">17-dione (</span><b><span style="font-family:Verdana;">6</span></b><span style="font-family:Verdana;">). Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-MS experiments. Substrate </span><b><span style="font-family:Verdana;">1</span></b><span style="font-family:Verdana;"> and its derivatives </span><b><span style="font-family:Verdana;">2</span></b></span><span style="font-family:Verdana;">-</span><b><span style="font-family:Verdana;">6</span></b><span style="font-family:""><span style="font-family:Verdana;"> were evaluated </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;"> for their urease and </span><span style="font-family:Verdana;">chymotrypsin</span><span style="font-family:Verdana;"> inhibitory properties. Compounds </span><b><span style="font-family:Verdana;">2</span></b><span style="font-family:Verdana;"> and </span><b><span style="font-family:Verdana;">3</span></b><span style="font-family:Verdana;"> were found to have strong urease activity with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> = 23.7 ± 0.17 and </span><span style="font-family:Verdana;">10.2 ± 0.28 </span></span><span style="font-family:Verdana;">μ</span><span style="font-family:Verdana;">m, respectively, as compared to the standard drug thiourea (IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> = 21.6 ± 0.12 </span><span style="font-family:Verdana;">μ</span><span style="font-family:""><span style="font-family:Verdana;">m). Compounds </span><b><span style="font-family:Verdana;">4</span></b><span style="font-family:Verdana;">, </span><b><span style="font-family:Verdana;">5</span></b><span style="font-family:Verdana;"> and </span><b><span style="font-family:Verdana;">6</span></b><span style="font-family:Verdana;"> showed good chymotrypsin activity with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> values of 6.4 ± 0.19, 15.6 ± 0.46 and 18.4 ± 0.65 </span></span><span style="font-family:Verdana;">μ</span><span style="font-family:""><span style="font-family:Verdana;">m, respectively, as compared to standard chymostatin with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> = 5.7 ± 0.14 </span></span><span style="font-family:Verdana;">μ</span><span style="font-family:Verdana;">m. These transformed metabolites may form the basis for the future development of new drugs against ulcer, inflammation, bacterial and viral diseases.</span>展开更多
文摘<span style="font-family:Verdana;">Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (</span><b><span style="font-family:Verdana;">1</span></b><span style="font-family:Verdana;">) with </span><i><span style="font-family:Verdana;">Fusarium lini</span></i><span> </span><span style="font-family:Verdana;">NRRL 2204 was carried out for the first time, yielding two new metabolites, 3,7</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-dihydroxy-19-norandrost-1,3,5-trien-17-one</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">(</span><b><span style="font-family:Verdana;">3</span></b><span style="font-family:Verdana;">) and 6</span><i><span style="font-family:Verdana;">α</span></i></span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;">10</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;">17</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-trihydroxy-19-nor-4-androsten-3-one</span><span style="font-family:""> </span><span style="font-family:""><span style="font-family:Verdana;">(</span><b><span style="font-family:Verdana;">4</span></b><span style="font-family:Verdana;">), along</span></span><span style="font-family:Verdana;"> with three known compounds, </span><span style="font-family:""><span style="font-family:Verdana;">3</span><b><span style="font-family:Verdana;">-</span></b><span style="font-family:Verdana;">hydroxy-19-norandrost-1,3,5-trien-17-one (</span><b><span style="font-family:Verdana;">2</span></b><span style="font-family:Verdana;">), 10</span></span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:""><span style="font-family:Verdana;">,</span><i> </i></span><span style="font-family:Verdana;">17</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:""><span style="font-family:Verdana;">-dihydroxy-19-nor-4-androsten-3-one (</span><b><span style="font-family:Verdana;">5</span></b><span style="font-family:Verdana;">) and</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">10</span><i><span style="font-family:Verdana;">β</span></i><span style="font-family:Verdana;">-hydroxy-19-nor-4-</span><span style="font-family:""> </span><span style="font-family:Verdana;">androsten-3</span><span style="font-family:Verdana;">,</span><span style="font-family:""><span style="font-family:Verdana;">17-dione (</span><b><span style="font-family:Verdana;">6</span></b><span style="font-family:Verdana;">). Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-MS experiments. Substrate </span><b><span style="font-family:Verdana;">1</span></b><span style="font-family:Verdana;"> and its derivatives </span><b><span style="font-family:Verdana;">2</span></b></span><span style="font-family:Verdana;">-</span><b><span style="font-family:Verdana;">6</span></b><span style="font-family:""><span style="font-family:Verdana;"> were evaluated </span><i><span style="font-family:Verdana;">in vitro</span></i><span style="font-family:Verdana;"> for their urease and </span><span style="font-family:Verdana;">chymotrypsin</span><span style="font-family:Verdana;"> inhibitory properties. Compounds </span><b><span style="font-family:Verdana;">2</span></b><span style="font-family:Verdana;"> and </span><b><span style="font-family:Verdana;">3</span></b><span style="font-family:Verdana;"> were found to have strong urease activity with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> = 23.7 ± 0.17 and </span><span style="font-family:Verdana;">10.2 ± 0.28 </span></span><span style="font-family:Verdana;">μ</span><span style="font-family:Verdana;">m, respectively, as compared to the standard drug thiourea (IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> = 21.6 ± 0.12 </span><span style="font-family:Verdana;">μ</span><span style="font-family:""><span style="font-family:Verdana;">m). Compounds </span><b><span style="font-family:Verdana;">4</span></b><span style="font-family:Verdana;">, </span><b><span style="font-family:Verdana;">5</span></b><span style="font-family:Verdana;"> and </span><b><span style="font-family:Verdana;">6</span></b><span style="font-family:Verdana;"> showed good chymotrypsin activity with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> values of 6.4 ± 0.19, 15.6 ± 0.46 and 18.4 ± 0.65 </span></span><span style="font-family:Verdana;">μ</span><span style="font-family:""><span style="font-family:Verdana;">m, respectively, as compared to standard chymostatin with IC</span><sub><span style="font-family:Verdana;">50</span></sub><span style="font-family:Verdana;"> = 5.7 ± 0.14 </span></span><span style="font-family:Verdana;">μ</span><span style="font-family:Verdana;">m. These transformed metabolites may form the basis for the future development of new drugs against ulcer, inflammation, bacterial and viral diseases.</span>