Liu Desheng, Ma Liying, Rong Xianguo, Kang Huihui, Liu Weizhong
Laboratory of Natural Drug Discovery and Research, College of Pharmacy, Binzhou Medical University, Yantai, China.
Front Microbiol. 2024 Nov 22;15:1495396. doi: 10.3389/fmicb.2024.1495396. eCollection 2024.
In recent decades, spiroketals which features with two rings joined by a spiro atom, have stimulated a great deal of researches for their diverse significant biological activities. Fungi are proved to be key reservoirs of structurally unique chemical skeletons. Up to date, [6,6]-spiroketals from fungal strains are still sporadically reported. Guided by UV information based on HPLC-DAD system, five unreported azaphilone-based [6,6]-spiroketals , named spirolones A-E, along with one known analogue, pestafolide A , were isolated from a productive saline soil derived fungus .
Their planar structures were solved through a comprehensive set of spectroscopic techniques including UV, IR, HRESIMS and 1D/2D NMR. The absolute configurations were determined by X-ray single-crystal diffractions or the modified Mosher's method. The misassignment of absolute configuration of pestafolide A was revised by X-ray crystallographic analysis in this study. All the isolated compounds were screened for antibacterial effect against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli based on the microplate approach and the cytotoxicity towards HepG2 and Hep3B cell lines based on MTT assay.
The results suggested that compound displayed some activity against P. aeruginosa and E. coli with MIC values of 35.00 μg/mL and 55.00 μg/mL, with MIC values of the positive control of streptomycin at 12.50 μg/mL and 8.00 μg/mL, respectively. Compound exhibited inhibitory effect against HepG2 cell line with IC50 value of 3.40 μM, and 8.14 μM against Hep3B cell line with doxorubincin as positive control. Compounds and may be capable of contribution for the development of new antibiotics or antitumor agents.
近几十年来，具有由一个螺原子连接两个环结构特征的螺缩酮，因其多样且显著的生物活性引发了大量研究。真菌被证明是结构独特化学骨架的关键来源。迄今为止，来自真菌菌株的[6,6]-螺缩酮仍有零星报道。基于高效液相色谱-二极管阵列检测（HPLC-DAD）系统的紫外信息指导下，从一种源自生产性盐渍土的真菌中分离出了5个未报道的基于氮杂蒽酮的[6,6]-螺缩酮，命名为螺旋酮A-E，以及一个已知类似物佩斯塔福利德A。
通过包括紫外、红外、高分辨电喷雾电离质谱（HRESIMS）和一维/二维核磁共振等一系列综合光谱技术解析其平面结构。通过X射线单晶衍射或改良的莫舍尔方法确定绝对构型。本研究通过X射线晶体学分析修正了佩斯塔福利德A绝对构型的错误归属。基于微孔板法筛选所有分离得到的化合物对铜绿假单胞菌、金黄色葡萄球菌和大肠杆菌的抗菌效果，基于MTT法筛选其对肝癌细胞系HepG2和Hep3B的细胞毒性。
结果表明，化合物对铜绿假单胞菌和大肠杆菌显示出一定活性，最低抑菌浓度（MIC）值分别为35.00 μg/mL和55.00 μg/mL，链霉素阳性对照的MIC值分别为12.50 μg/mL和8.00 μg/mL。化合物对肝癌细胞系HepG2表现出抑制作用，半数抑制浓度（IC50）值为3.40 μM，对Hep3B细胞系的IC50值为8.14 μM，阿霉素作为阳性对照。化合物和可能有助于新型抗生素或抗肿瘤药物的开发。
