Antiviral Merosesquiterpenoids Produced by the Antarctic Fungus Aspergillus ochraceopetaliformis SCSIO 05702

• Published in: Journal of natural products (Washington, D.C.) Vol. 79; no. 1; pp. 59 - 65
• Main Authors: Wang, Junfeng, Wei, Xiaoyi, Qin, Xiaochu, Tian, Xinpeng, Liao, Li, Li, Kemin, Zhou, Xuefeng, Yang, Xianwen, Wang, Fazuo, Zhang, Tianyu, Tu, Zhengchao, Chen, Bo, Liu, Yonghong
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 22.01.2016; Amer Chemical Soc
• Subjects: Antarctic Regions; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - isolation & purification; Anti-Bacterial Agents - pharmacology; Antiviral Agents - chemistry; Antiviral Agents - isolation & purification; Antiviral Agents - pharmacology; Chemistry, Medicinal; Crystallography, X-Ray; Influenza A Virus, H1N1 Subtype - drug effects; Influenza A Virus, H3N2 Subtype - drug effects; Inhibitory Concentration 50; Life Sciences & Biomedicine; Marine Biology; Molecular Conformation; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pharmacology & Pharmacy; Plant Sciences; Pyrones - chemistry; Pyrones - isolation & purification; Pyrones - pharmacology; Science & Technology; Sesquiterpenes - chemistry; Sesquiterpenes - isolation & purification; Sesquiterpenes - pharmacology; Soil Microbiology; Antarctic Regions; ACYLTRANSFERASE; METABOLITES; POTENT; ORALLY BIOAVAILABLE INHIBITOR; PENICILLIUM; ACETYLCHOLINESTERASE; BIOSYNTHESIS; PYRIPYROPENE; ALPHA-PYRONE; SESQUITERPENOIDS
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00650

Five new highly oxygenated α-pyrone merosesquiterpenoids, ochraceopones A–E (1–5), together with one new double bond isomer of asteltoxin, isoasteltoxin (6), and two known asteltoxin derivatives, asteltoxin (7) and asteltoxin B (8), were isolated from an Antarctic soil-derived fungus, Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were determined through extensive spectroscopic analysis, CD spectra, quantum mechanical calculations, and X-ray single-crystal diffraction. Ochraceopones A–D (1–4) are the first examples of α-pyrone merosesquiterpenoids possessing a linear tetracyclic carbon skeleton, which has not been previously described. All the isolated compounds were tested for their antiviral, cytotoxic, antibacterial, and antitubercular activities. Among these compounds, ochraceopone A (1), isoasteltoxin (6), and asteltoxin (7) exhibited antiviral activities against the H1N1 and H3N2 influenza viruses with IC50 values of >20.0/12.2 ± 4.10, 0.23 ± 0.05/0.66 ± 0.09, and 0.54 ± 0.06/0.84 ± 0.02 μM, respectively. A possible biosynthetic pathway for ochraceopones A–E (1–5) was proposed.