关键词: Atranones Cardiomyocyte protective activity Dolabellanes Stachybotrys chartarum Structural elucidation

Mesh : Animals Stachybotrys / chemistry Anthozoa / microbiology chemistry Diterpenes / pharmacology chemistry isolation & purification Myocytes, Cardiac / drug effects Molecular Structure Dose-Response Relationship, Drug Cold Temperature Rats Cardiotonic Agents / pharmacology chemistry isolation & purification Molecular Conformation Phosphatidylinositol 3-Kinases / metabolism

来  源:   DOI:10.1016/j.phytochem.2024.114199

Abstract:
Five undescribed atranones, namely atranones V-Z (1-5), three undescribed dolabellane-type diterpenoids, namely stachatranones D-F (7-9), together with four known congeners (6 and 10-12), were obtained from a coral-associated strain of the toxigenic fungus Stachybotrys chartarum. Their structures were elucidated via extensive spectroscopic analyses, mainly including the HRESIMS and NMR data, single-crystal X-ray diffraction analysis, electronic circular dichroism calculation, and [Mo2(OAc)4] induced circular dichroism spectrum. The cardiomyocyte protective activity assay revealed that compound 9 significantly ameliorated cold ischemic injury at 24 h post cold ischemia (CI) in a dose-dependent manner. Moreover, compound 9 prevented CI induced dephosphorylation of phosphatidylinositol-3-kinase and RAC-α serine/threonine-protein kinase at 12 h post CI in a dose-dependent manner. In this work, the undescribed compound 9 could significantly protect cardiomyocytes against cold ischemic injury, highlighting the promising potential to be designed and developed as a novel cardioprotectant in heart transplant medicine.
摘要:
五个未描述的atranones,即atranonesV-Z(1-5),三种未描述的dolabellane型二萜,即stachatranonesD-F(7-9),连同四个已知的同源物(6和10-12),是从与产毒真菌Stachybotryschartarum的珊瑚相关菌株中获得的。通过广泛的光谱分析阐明了它们的结构,主要包括HRESIMS和NMR数据,单晶X射线衍射分析,电子圆二色性计算,和[Mo2(OAc)4]诱导的圆二色光谱。心肌细胞保护活性测定显示,化合物9在冷缺血(CI)后24小时以剂量依赖性方式显著改善冷缺血损伤。此外,化合物9预防CI在CI后12小时以剂量依赖性方式诱导磷脂酰肌醇-3-激酶和RAC-α丝氨酸/苏氨酸蛋白激酶的去磷酸化。在这项工作中,未描述的化合物9可以显著保护心肌细胞免受冷缺血损伤,强调了作为心脏移植医学中新型心脏保护剂的设计和开发潜力。
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