Bioactive Pyranones Isolated From the Mangrove-Associated Endophytic Fungus Aspergillus sp. H6a

Area of Science:

• Natural Product Chemistry
• Medicinal Chemistry
• Mycology

Background:

• Mangrove endophytic fungi are a rich source of novel bioactive compounds.
• Aspergillus species are known producers of diverse secondary metabolites with potential pharmaceutical applications.
• Developing new anticancer agents is crucial, especially those effective against drug-resistant cancer cells.

Purpose of the Study:

• To isolate and characterize new compounds from the mangrove endophytic fungus Aspergillus sp. H6a.
• To evaluate the cytotoxic activity of isolated compounds against A549 lung cancer cells.
• To investigate the potential of active compounds in overcoming cisplatin resistance.

Main Methods:

• Isolation and structure elucidation of compounds using spectroscopic data (NMR, MS) and ECD analysis.
• Cytotoxicity assays (CCK-8) to determine IC50 values against A549 and A549/DDP cells.
• Combination studies to assess synergistic effects with cisplatin (DDP).

Main Results:

• Six new compounds (four naphtho-γ-pyrone dimers, one monomer, one coumarin) and 12 known analogues were isolated.
• Compound 10 exhibited potent cytotoxicity against A549 cells (IC50 = 11.27 µM), comparable to cisplatin.
• Compound 10 demonstrated significant activity against DDP-resistant A549/DDP cells (IC50 = 12.58 µM) and enhanced DDP efficacy in combination therapy.

Conclusions:

• The study expands the known chemical diversity of Aspergillus endophytes from mangroves.
• Compound 10 is a promising candidate for anticancer drug development, particularly for overcoming cisplatin resistance.
• Further investigation into compound 10's mechanism of action and therapeutic potential is warranted.