Bashyal Bharat P, Wijeratne E M Kithsiri, Tillotson Joseph, Arnold A Elizabeth, Chapman Eli, Gunatilaka A A Leslie
Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona , 250 E. Valencia Road, Tucson, Arizona 85706, United States.
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , Tucson, Arizona 85721, United States.
J Nat Prod. 2017 Feb 24;80(2):427-433. doi: 10.1021/acs.jnatprod.6b00960. Epub 2017 Jan 31.
Investigation of Alternaria sp. AST0039, an endophytic fungus obtained from the leaf tissue of Astragalus lentiginosus, led to the isolation of (-)-(10E,15S)-4,6-dichloro-10(11)-dehydrocurvularin (1), (-)-(10E,15S)-6-chloro-10(11)-dehydrocurvularin (2), (-)-(10E,15S)-10(11)-dehydrocurvularin (3), and alterperylenepoxide A (4) together with scytalone and α-acetylorcinol. Structures of 1 and 4 were established from their spectroscopic data, and the relative configuration of 4 was determined with the help of nuclear Overhauser effect difference data. All metabolites were evaluated for their cytotoxic activity and ability to induce heat-shock and unfolded protein responses. Compounds 2 and 3 exhibited cytotoxicity to all five cancer cell lines tested and increased the level of the pro-apoptotic transcription factor CHOP, but only 3 induced the heat-shock response and caused a strong unfolded protein response.
对从绵毛黄芪叶片组织中获得的内生真菌链格孢属AST0039进行研究，从中分离出了(-)-(10E,15S)-4,6-二氯-10(11)-脱氢弯孢霉菌素(1)、(-)-(10E,15S)-6-氯-10(11)-脱氢弯孢霉菌素(2)、(-)-(10E,15S)-10(11)-脱氢弯孢霉菌素(3)和变过氧二萘嵌苯A(4)，以及细胞松弛素和α-乙酰基苔黑酚。根据1和4的光谱数据确定了它们的结构，并借助核Overhauser效应差值数据确定了4的相对构型。对所有代谢产物的细胞毒性活性以及诱导热休克和未折叠蛋白反应的能力进行了评估。化合物2和3对所测试的所有五种癌细胞系均表现出细胞毒性，并提高了促凋亡转录因子CHOP的水平，但只有3诱导了热休克反应并引发了强烈的未折叠蛋白反应。
