Discovery of a Dimeric Zinc Complex and Five Cyclopentenone Derivatives from the Sponge-Associated Fungus Aspergillus ochraceopetaliformis

In devotion to investigating
structurally novel and biologically
active marine natural products, a dimer of a zinc complex, dizinchydroxyneoaspergillin
(1), aspernones A–E (2–6), five cyclopentenone derivatives together with known polyketides
(7–10), and neoaspergillic acid analogues
(11–14) were isolated from the sponge-associated
fungus Aspergillus ochraceopetaliformis SCSIO 41018. Their structures were elucidated on the basis of spectroscopic
analysis, electronic circular dichroism (ECD) analysis, and X-ray
diffraction. Dizinchydroxyneoaspergillin (1) displayed
significant bactericide effects toward methicillin-resistant Staphyloccocus aureus, Staphyloccocus
aureus, Enterococcus faecalis, Acinetobacter baumannii, and Klebsiella pneumonia with MIC values of 0.45–7.8
μg/mL and moderate in vitro cytotoxic activities against the
K562, BEL-7402, and SGC-7901 cell lines with IC50 values
of 12.88 ± 0.14, 15.83 ± 0.23, and 15.08 ± 0.62 μM,
respectively. This is the first time to report the dimer of the zinc
complex of hydroxyneoaspergillic acid conjunction at Zn–N-4
by a coordination bond. Additionally, compound 1 displayed
significant antibacterial and cytotoxic activities, which would be
a promising drug lead and could attract much attention from both chemists
and pharmacists.

为探究结构新颖且具有生物活性的海洋天然产物，研究团队从海绵共附生真菌赭曲霉（Aspergillus ochraceopetaliformis）SCSIO 41018中分离得到一类锌配合物二聚体——二锌羟基新曲霉素（1）、aspernones A–E（2–6，共5个环戊烯酮衍生物）、已知聚酮类化合物（7–10）以及新曲霉酸类似物（11–14）。上述化合物的结构通过光谱分析、电子圆二色性（electronic circular dichroism，ECD）分析与X射线衍射得以解析。二锌羟基新曲霉素（1）对耐甲氧西林金黄色葡萄球菌、金黄色葡萄球菌、粪肠球菌、鲍曼不动杆菌及肺炎克雷伯菌均表现出显著杀菌活性，最低抑菌浓度（MIC）范围为0.45–7.8 μg/mL；同时对K562、BEL-7402与SGC-7901细胞株展现出中等体外细胞毒性，半数抑制浓度（IC50）分别为12.88 ± 0.14、15.83 ± 0.23及15.08 ± 0.62 μM。本研究首次报道了通过配位键以Zn–N-4模式连接的羟基新曲霉酸锌配合物二聚体。此外，化合物1兼具显著抗菌与细胞毒性活性，是极具潜力的药物先导化合物，将受到化学与药学领域研究者的广泛关注。