Insights into Ergochromes of the Plant Pathogen <i>Claviceps purpurea</i>

Claviceps purpurea is an ergot fungus known for its neurotropic alkaloids, which have been identified as the main cause of ergotism, a livestock and human disease triggered by ergot consumption. Tetrahydroxanthone dimers, the so-called ergopigments, presumably also contribute to this toxic effect. Overexpression of the cluster-specific transcription factor responsible for the formation of these pigments in C. purpurea led to the isolation of three new metabolites (8–10). The new pigments were characterized utilizing HRMS, NMR techniques, and CD spectroscopy and shown to be xanthone dimers. Secalonic acid A and its 2,4′- and 4,4′-linked isomers were also isolated, and their absolute configuration was investigated. The contribution of secalonic acid A, its isomers, and new metabolites to the toxicity of C. purpurea was investigated in HepG2 and CCF-STTG1 cells. Along with cytotoxic properties, secalonic acid A was found to inhibit topoisomerase I and II activity.紫麦角菌（Claviceps purpurea）是一类麦角真菌，因其合成的嗜神经生物碱（neurotropic alkaloids）而被广泛知晓——这类生物碱被确认为引发麦角中毒（ergotism）的主要致病因子，麦角中毒是一种因摄入麦角而诱发的人畜共患病。所谓的麦角色素（ergopigments）即四氧杂蒽酮二聚体（tetrahydroxanthone dimers），据推测也参与了该毒性效应的介导。在紫麦角菌中过表达负责调控这类色素生物合成的簇特异性转录因子（cluster-specific transcription factor）后，研究人员成功分离得到3种全新代谢产物（8~10）。 研究人员通过高分辨质谱（HRMS）、核磁共振波谱（NMR）技术以及圆二色谱（CD spectroscopy）对上述新型色素进行了结构表征，证实其为氧杂蒽酮二聚体。此外，研究人员还分离得到了司拉诺酸A（secalonic acid A）及其2,4′-、4,4′-位连接的异构体，并对其绝对构型开展了研究。以HepG2细胞与CCF-STTG1细胞为体外模型，研究人员探究了司拉诺酸A、其异构体以及上述新型代谢产物对紫麦角菌毒性的贡献。除具备细胞毒性外，研究还发现司拉诺酸A可抑制拓扑异构酶I和II（topoisomerase I and II）的活性。