Phenylhydrazone Alkaloids from the Deep-Sea Cold Seep Derived Fungus <i>Talaromyces amestolkiae</i> HDN21-0307
Jiajin Wu, Wenxue Wang, Yuhuan Yang, Mudassir Shah, Jixing Peng, Luning Zhou, Guojian Zhang, Qian Che, Jing Li, Tianjiao Zhu, Dehai Li
Abstract
Alkaloids with a phenylhydrazone architecture are rarely found in nature. Four unusual phenylhydrazone alkaloids named talarohydrazones A–D ( 1 – 4 ) were isolated from the deep-sea cold seep derived fungus Talaromyces amestolkiae HDN21-0307 using the one strain–many compounds (OSMAC) approach and MS/MS-based molecular networking (MN) combined with network annotation propagation (NAP) and the unsupervised substructure annotation method MS2LDA. Their structures were elucidated by spectroscopic data analysis, single-crystal X-ray diffraction, and quantum chemical calculations. Talarohydrazone A ( 1 ) possessed an unusual skeleton combining 2,4-pyridinedione and phenylhydrazone. Talarohydrazone B ( 2 ) represents the first natural phenylhydrazone-bearing azadophilone. Bioactivity evaluation revealed that compound 1 exhibited cytotoxic activity against NCI-H446 cells with an IC 50 value of 4.1 μM. In addition, compound 1 displayed weak antibacterial activity toward Staphylococcus aureus with an MIC value of 32 μg/mL.