Landomycins P-W, cytotoxic angucyclines from Streptomyces cyanogenus S-136.
Landomycins P-W, cytotoxic angucyclines from Streptomyces cyanogenus S-136.
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DOI：
10.1021/np100469y
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发表时间：
2011-01-28
影响因子：
5.1
通讯作者：
Rohr J
中科院分区：
文献类型：
--
作者：
Shaaban KA;Srinivasan S;Kumar R;Damodaran C;Rohr J
产蓝链霉菌S-136是已报道的地霉素A-D的产生菌。对该菌株的次要产物进行分析，分离并鉴定了8个新的同系物，命名为地霉素P-W(5，6，3，17，9，10，15，7)，以及其他10个已知的环素类化合物。根据核磁共振和质谱学数据确定了新化合物的结构。用MCF-7(雌激素敏感的)和MDA-231(雌激素不敏感的)乳腺癌细胞株测定这些血管环素的活性。细胞存活率测定结果表明，在MCF-7和MDA-231细胞活性测定中，脱水红霉素(2)、红霉素A(11)和红霉素A(16)的联合活性最好，其中2的联合作用最强，11和16的联合作用最强。这些数据表明，一些苷元等同于含有最长糖链的主要产物16。具体而言，脱水地霉酮(2)对MCF-7细胞的抑制作用最强(IC_(50)=1.8μM)。糖基较短的化合物对MCF-7的抑制作用较弱。事实上，最活跃的土霉素要么有很长的五糖或六糖链，要么根本没有糖，这表明大的化合物可能通过不同的作用模式而不是它们的小的无糖同系物。这些结果为深入了解土霉素的构效关系(SAR)提供了更多的信息。
Streptomyces cyanogenus S-136 is the producer of previously reported landomycins A – D. An analysis of minor products of the strain led to isolation and structure elucidation of eight new congeners, named landomycins P – W (5, 6, 3, 17, 9, 10, 15, 7), along with ten other known angucyclin(on)es. The structures of the new compounds were established from their NMR and mass spectrometry data. The activity of these angucyclin( on)es was determined using MCF-7 (estrogen responsive) and MDA-231 (estrogen refractory) breast cancer cell lines. Cell viability assays showed that anhydrolandomycinone (2), landomycinone (11) and landomycin A (16) showed the best combined activities in both MCF-7 and MDA-231 assays with 2 being the most potent in the former and 11 and 16 in the latter. These data reveal that some of the aglycones are equipotent to the principle product 16, which contains the longest saccharide chain. Specifically, anhydrolandomycinone (2) was the most active against MCF-7 cells (IC50=1.8 μM). Compounds with shorter saccharidal moieties were less potent against MCF-7. The fact that the most active landomycins either have long penta- or hexasaccharide chains or no sugars at all suggests that the large compounds may act by a different mode of action than their small sugar-free congeners. The results presented here provide more insights into the structure activity relationship (SAR) of landomycins.
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影响因子：
5.1
作者：
Potterat, Olivier;Puder, Carsten;Kauschke, Stefan G.
通讯作者：
Kauschke, Stefan G.
影响因子：
5.1
作者：
Fotso, Serge;Mahmud, Taifo;Proteau, Philip. J.
通讯作者：
Proteau, Philip. J.
影响因子：
3.2
作者：
Luzhetskyy, A;Zhu, LL;Bechthold, A
通讯作者：
Bechthold, A
影响因子：
3.6
作者：
Krohn, K;Bernhard, S;Hayat, N
通讯作者：
Hayat, N
影响因子：
3.6
作者：
Roush, WR;Neitz, RJ
通讯作者：
Neitz, RJ