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1.
Adv Sci (Weinh) ; : e2401869, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959395

RESUMO

Ionic conductive hydrogels (ICHs) have recently gained prominence in biosensing, indicating their potential to redefine future biomedical applications. However, the integration of these hydrogels into sensor technologies and their long-term efficacy in practical applications pose substantial challenges, including a synergy of features, such as mechanical adaptability, conductive sensitivity, self-adhesion, self-regeneration, and microbial resistance. To address these challenges, this study introduces a novel hydrogel system using an imidazolium salt with a ureido backbone (UL) as the primary monomer. Fabricated via a straightforward one-pot copolymerization process that includes betaine sulfonate methacrylate (SBMA) and acrylamide (AM), the hydrogel demonstrates multifunctional properties. The innovation of this hydrogel is attributed to its robust mechanical attributes, outstanding strain responsiveness, effective water retention, and advanced self-regenerative and healing capabilities, which collectively lead to its superior performance in various applications. Moreover, this hydrogel  exhibited broad-spectrum antibacterial activity. Its potential for biomechanical monitoring, especially in tandem with contact and noncontact electrocardiogram (ECG) devices, represents a noteworthy advancement in precise real-time cardiac monitoring in clinical environments. In addition, the conductive properties of the hydrogel make it an ideal substrate for electrophoretic patches aimed at treating infected wounds and consequently enhancing the healing process.

2.
Eur J Med Chem ; 265: 116064, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38159483

RESUMO

The enzyme FabH plays a critical role in the initial step of fatty acid biosynthesis, which is vital for the survival of bacteria. As a result, FabH has emerged as an appealing target for the development of novel antibacterial agents. In this study, employing the chemical proteomics method, we validated the previously identified skeleton amide derivatives bearing dioxygenated rings, potentially formed through metabolic processes. Building upon the proteomics findings, we then synthesized and evaluated 32 compounds containing N-heterocyclic amides for their antimicrobial activity for future optimizing the deoxygenated amides. Several compounds demonstrated potent antimicrobial properties with low toxicity, particularly compound 25, which exhibited remarkable potential as an agent with an MIC range of 1.25-3.13 µg/mL against the tested bacterial strains and an IC50 of 2.0 µM against E. coli-derived FabH. Furthermore, we evaluated nine analogues with relatively low MIC values through cytotoxicity and hemolytic activity assessments, Lipinski's rule-of-five criteria, and in silico ADMET predictions to ascertain their druggability potential. Notably, a detailed docking simulation was performed to investigate the binding interactions of compound 25 within the binding pocket of E. coli FabH, which encouragingly revealed strong binding interactions. Based on our findings, compound 25 emerges as the optimal candidate for in vivo therapy aimed at treating infected skin defects. Remarkably, the application of compound 25 demonstrated a significant reduction in the duration of wound infection and notably accelerated the healing process of infected wounds, achieving an impressive 94 % healing rate by day 10.


Assuntos
Antibacterianos , Proteínas de Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli , Bactérias , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
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