NMR-Based Structural Elucidation of a New Dihydroisocoumarin and Related Polyketides From a Mangrove-Derived Fusarium sp.

Antimicrobial resistance (AMR) remains one of the greatest global public health challenges of the 21st century, compromising the effectiveness of current therapies and highlighting the urgent need for new antibacterial agents. Natural products from bacteria and filamentous fungi continue to represent an invaluable source of structurally diverse bioactive metabolites. In this study, a library of 56 extracts obtained from mangrove-associated ascomycetes was screened against a panel of multidrug-resistant bacterial pathogens. Bioactivity data were integrated with LC-MS/MS-based molecular networking to prioritize extracts for chemical investigation. This approach identified Fusarium sp. IQ-1921 as one of the most promising candidates, leading to the isolation of a new dihydroisocoumarin (1) and four known analogues (2-5). The structures of all isolated metabolites were elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HRMS). All compounds were evaluated against multidrug-resistant strains of Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Staphylococcus aureus. Compounds 1 and 3-5 exhibited moderate antibacterial activity, with compound 1 displaying the broadest inhibitory profile. These findings demonstrate the effectiveness of integrating metabolomics with bioactivity-guided prioritization for the discovery of antibacterial natural products and further highlight the indispensable role of NMR spectroscopy in the structural elucidation of closely related fungal metabolites.