Azaphilone Derivatives from the Fungus Coniella fragariae Inhibit NF-κB Activation and Reduce Tumor Cell Migration.

Abstract

Seven new azaphilones, coniellins A-G (1-7), were obtained from the fungus Coniella fragariae that had been isolated from goose dung. Their structures were elucidated by analysis of 1D and 2D NMR as well as HRESIMS data. TDDFT-ECD calculation was used to determine the absolute configuration of 1, while Mosher's method was applied to determine the absolute configuration of 5. While displaying only moderate cytotoxicity, compound 1 exhibited significant inhibition of NF-κB activation in the triple negative breast cancer cell line MDA-MB-231 with an IC50 value of 4.4 μM. Moreover, compounds 1, 4, and 5 clearly reduced tumor cell migration. Compound 1 was the most active derivative tested in this assay and displayed 60% inhibition of tumor cell migration at a dose of 5 μM and 98% inhibition at 10 μM after 24 h.

• Authors: Haiqian Yu, Julia Sperlich, Attila Mándi, Tibor Kurtán, Haofu Dai, Nicole Teusch, Zhi-Yong Guo, Kun Zou, Zhen Liu, Peter Proksch
• Journal: Journal of natural products (J Nat Prod) Vol. 81 Issue 11 Pg. 2493-2500 (11 26 2018) ISSN: 1520-6025 [Electronic] United States
• PMID: 30354103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzopyrans
• NF-kappa B
• Pigments, Biological
• azaphilone

Topics

• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Ascomycota (chemistry)
• Benzopyrans (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Migration Inhibition
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Structure
• NF-kappa B (antagonists & inhibitors)
• Pigments, Biological (chemistry, isolation & purification, pharmacology)