Hymecromone

The excessive use of antibiotics has accelerated the rapid development and spread of drug-resistant bacteria, posing a severe threat to public health security. It is imperative to develop simple yet effective novel antimicrobial agents to replace antibiotic usage. Natural products typically possess a broad spectrum of pharmacological activities and are often associated with lower toxicity and fewer side effects. Consequently, the development of natural product-based antimicrobial agents presents a promising avenue for effectively replacing existing antibiotics. Building upon this foundation, leveraging the optical properties of natural product derivatives for dual-function detection of biomarkers is of significant importance. In this work, we propose a multi-component synergistic strategy involving the conjugation of the natural product rhein with the pharmacologically active molecule 4-methylumbelliferone through a chemical reaction, constructing the fluorescent probe Rhe-MU. This probe not only enabled the rapid fluorescence response and naked-eye detection of H₂S (manifested by a distinct solution color change from yellow to pink and a fluorescence shift from yellow to blue) but also facilitated the successful preparation of a bifunctional composite hydrogel (Rhe-MU-Gel) via non-covalent assembly with the intrinsically antimicrobial amino acid hydrogel Fmoc-F. Rhe-MU-Gel exhibited enhanced inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA) by integrating the synergistic antibacterial effects of rhein, 4-MU, and Fmoc-F. Concurrently, its superior biocompatibility overcame the inherent hydrophobicity limitations associated with traditional rhein derivatives, while retaining the capability for the visual detection of H₂S in vitro. This work successfully constructed a hydrogel system integrating dual "detection-antibacterial" functionality. The proposed natural product-based multi-component integration strategy establishes a novel design strategy for bifunctional fluorescent probes and next-generation antimicrobial agents. It demonstrates significant potential as a promising therapeutic alternative to conventional antibiotics for effectively combating drug-resistant bacterial infections and addressing the critical challenge of antimicrobial resistance.