Cinnamic‐Hydroxamic‐Acid Derivatives Exhibit Antibiotic, Anti‐Biofilm, and Supercoiling Relaxation Properties by Targeting Bacterial Nucleoid‐Associated Protein HU
Year: 2025
Type: article
Abstract: Finding novel compounds and drug targets is crucial for antibiotic development. The nucleoid‐associated protein HU plays a significant role in bacterial DNA metabolism, supercoiling, and biofilm formation, making it a promising new target. In this work, structure‐based screening and identified cinnamic‐hydroxamic‐acid derivatives (CHADs) are conducted as HU inhibitors, with a minimum inhibitory concentration (MIC) of as low as 12 µg mL −1 against a range of pathogenic bacteria. CHADs induce nucleoid deformation, preventing bacterial division and inhibiting growth. They exhibit low toxicity in mice and effectively treat infections in mouse models. Additionally, CHADs possess anti‐biofilm activity and supercoiling relaxation properties, countering bacterial stress responses to antibiotics. They suppress changes in gene expression required for optimal stress responses, resulting in synergistic effects with other antibiotics. Thus, CHADs represent a new class of antibiotics that inhibit bacterial stress responses by co‐targeting biofilm formation and DNA supercoiling.
Source: Advanced Science
Institutions: First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Imperial College London, Hainan Medical University, Huazhong University of Science and Technology, Beijing University of Chemical Technology, Chinese Academy of Sciences, Wuhan Institute of Virology, University of Health and Rehabilitation Sciences
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,730
OpenAlex ID: W4416530424