Xu An, Xu Xiang-Nan, Zhang Mi, Li Chun-Lian, Liu Li, Fu De-Yuan
Clinical Medical College, Yangzhou University, Yangzhou, China.
Department of Thyroid and Breast Surgery, Northern Jiangsu People's Hospital, Yangzhou, China.
Front Microbiol. 2022 Jul 22;13:959754. doi: 10.3389/fmicb.2022.959754. eCollection 2022.
Marine-derived microorganisms possess the unique metabolic pathways to produce structurally novel secondary metabolites with potent biological activities. In this study, bioactivity-guided isolation of the marine deep-sea-derived fungus DS720 led to the characterization of four indole alkaloids (compounds -) and four polyketides (compounds -), such as two new indoles, flavonoids A () and B () with a C-6 reversed prenylation, and a new azaphilone, flaviazaphilone A (). Their chemical structures were unambiguously established by an extensive interpretation of spectroscopic data, such as 1D/2D NMR and HRESIMS data. The absolute configurations of the new compound were solved by comparing the experimental and calculated Electronic Circular Dichroism (ECD) spectra. Since sufficient amount of flavonoids A () was obtained, was subjected to a large-scale cytotoxic activity screening against 20 different human tumor cell lines. The results revealed that showed broad-spectrum cytotoxicities against HeLa, 5637, CAL-62, PATU8988T, A-375, and A-673 cell lines, with the inhibition rates of more than 90%. This study indicated that the newly discovered indole alkaloid may possess certain potential for the development of lead compounds in the future.
海洋来源的微生物具有独特的代谢途径，可产生结构新颖且具有强大生物活性的次生代谢产物。在本研究中，通过生物活性导向分离海洋深海来源真菌DS720，鉴定出四种吲哚生物碱（化合物 - ）和四种聚酮化合物（化合物 - ），例如两种新的吲哚、具有C - 6反式异戊烯基化的黄酮类化合物A（）和B（），以及一种新的氮杂蒽酮类化合物黄酮氮杂蒽酮A（）。通过对光谱数据（如1D/2D NMR和HRESIMS数据）的广泛解读，明确确定了它们的化学结构。通过比较实验和计算的电子圆二色光谱（ECD），解析了新化合物的绝对构型。由于获得了足够量的黄酮类化合物A（），对其针对20种不同人类肿瘤细胞系进行了大规模细胞毒性活性筛选。结果表明，其对HeLa、5637、CAL - 62、PATU8988T、A - 375和A - 673细胞系表现出广谱细胞毒性，抑制率超过90%。本研究表明，新发现的吲哚生物碱未来可能具有开发先导化合物的一定潜力。
