NIR-II/pH Dual Responsive CuHDB@CaP Nanospheres as a Self-Cascading Catalytic Platform for Highly Efficient Combating Bacterial Infections DOI
Bo Li, Zongchao Jia, Bingyan Li

et al.

ACS Applied Nano Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

The misuse of antibiotics has led to a dramatic increase in bacterial resistance, creating an urgent need for efficient antimicrobial agents with multiple mechanisms action. In this study, Cu was modified berberine derivatives, and core–shell structure successfully developed, resulting light/pH-responsive CuHDB@CaP nanotherapeutic platform. It achieves controlled release CuHDB nanozymes, CaP, which is highly stable neutral or alkaline environments, preventing leakage effectively "switching off" the activity nanozymes. Bacterial metabolism, produces lactic keto acids, lowers pH wound microenvironment. Additionally, exposure 1064 nm near-infrared (NIR) light causes CaP shell collapse, releasing nanozymes on" their enzyme-like activity. This enables platform be both safe efficient. exhibits not only strong photothermal effect but also enhanced glutathione oxidase (GSHOx)-like peroxidase (POD)-like enzyme activities. GSHOx-like contributes generation H2O2, its excellent H2O2 affinity allows it efficiently catalyze conversion sufficient amount •OH through POD-like self-cascading catalytic does require introduction additional promotes consumption GSH infection can kill up 99.0% MRSA AmprE. coli, inhibit biofilm formation without emergence drug exhibit negligible cytotoxicity hemolysis. Treatment experiments mouse models showed that combined NIR could treat infections accelerate healing minimal toxicity normal tissue cells, demonstrating potential clinical treatment skin infections.

Language: Английский

Discovery of Quinazolone Pyridiniums as Potential Broad-Spectrum Antibacterial Agents DOI Creative Commons
Jie Dai,

Qianyue Li,

Ziyi Li

et al.

Molecules, Journal Year: 2025, Volume and Issue: 30(2), P. 243 - 243

Published: Jan. 9, 2025

The overprescription of antibiotics in medicine and agriculture has accelerated the development spread antibiotic resistance bacteria, which severely limits arsenal available to clinicians for treating bacterial infections. This work discovered a new class heteroarylcyanovinyl quinazolones quinazolone pyridiniums surmount increasingly severe resistance. Bioactive assays manifested that highly active compound 19a exhibited strong inhibition against MRSA Escherichia coli with extremely low MICs 0.5 μg/mL, being eightfold more than norfloxacin (MICs = 4 μg/mL). rapid bactericidal properties displayed imperceptible trends, negligible hemolytic toxicity, effective biofilm inhibitory effects. Preliminary explorations on antibacterial mechanisms revealed could cause membrane damage, embed intracellular DNA hinder replication, induce metabolic dysfunction. Surprisingly, was found trigger conformational change PBP2a open site, might account its high MRSA. In addition, little effect molecule production reactive oxygen species indicated death not caused by oxidative stress. above comprehensive analyses highlighted large potential as multitargeting broad-spectrum agents.

Language: Английский

Citations

2
Benzo-α-pyrone-derived multitargeting actions to enhance the antibacterial performance of sulfanilamides against Escherichia coli DOI
Yixin Wang, Haoran Wang,

Jiang-Sheng Zhao

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 158, P. 108339 - 108339

Published: March 5, 2025

Language: Английский

Citations

2
Design, Synthesis, and Bioactivity Evaluation of Novel 1-Methyl-2-phenylpyridin-1-ium Derivatives as Broad-Spectrum FtsZ Inhibitors DOI
Yang-Chun Ma,

Yue Kong,

Hang Ding

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

To address the threat of bacterial infections in animal husbandry, a novel class 1-methyl-2-phenylpyridin-1-ium derivatives has been designed and synthesized as broad-spectrum antibacterial agents to counteract increasing multidrug resistance. Biological assays revealed that compounds 4n, 16b, 16c, 16e exhibited superior inhibition S. aureus ATCC25923 (MICs = 0.0625–0.5 μg/mL) A. baumannii ATCC19606 1–4 compared linezolid vancomycin. Mechanistic studies promoted FtsZ polymerization, disrupted proton gradients, increased membrane permeability. Hemolytic toxicity assessments confirmed favorable biological safety profile 16e. In vivo using mouse model bacteremia demonstrated efficacy linezolid. Molecular dynamics simulations showed could maintain protein T state, which was conducive polymerization. These results provide new therapeutic strategies deal with emerging resistance husbandry.

Language: Английский

Citations

1
Identification of CH2-linker modified desfluoroquinolone-aminopyrimidine hybrids to combat antibiotic-resistant gram-positive bacteria DOI
Yue Hu, Xinghua Xu, Jiayi Chen

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 161, P. 108496 - 108496

Published: April 21, 2025

Language: Английский

Citations

1
Identification of Ch2-Linker Modified Desfluoroquinolone-Aminopyrimidine Hybrids to Combat Antibiotic-Resistant Gram-Positive Bacteria DOI
Qiuqin He, Yue Hu, Xinghua Xu

et al.

Published: Jan. 1, 2025

Language: Английский

Citations

0
Synthesis and antimicrobial evaluation of novel quaternary quinolone derivatives with low toxicity and anti-biofilm activity DOI

Ye Qu,

Chen Gao,

Ruirui Li

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 291, P. 117591 - 117591

Published: April 8, 2025

Language: Английский

Citations

0
Identification of hydroxyphenyl cyanovinyl thiazoles as new structural scaffold of potential antibacterial agents DOI

Lu Xing,

Shaolin Zhang, Cheng‐He Zhou

et al.

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown, P. 130258 - 130258

Published: April 1, 2025

Language: Английский

Citations

0
Natural Coumarin‐Hybridized Thiazolylbenzonitriles as New Structural Scaffolds to Exert Potentially Multitargeting Supramolecular Antibacterial Behavior DOI

Qianyue Li,

Chun‐Mei Zeng,

Qianming Chen

et al.

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Comprehensive Summary A unique type of natural coumarin skeleton‐based thiazolylbenzonitriles as novel structural scaffolds to exert potential multitargeting supramolecular antibacterial behavior was developed for the first time from resorcinol through multi‐step reactions. All new compounds were characterized by NMR and HRMS spectra. Structure‐activity relationships revealed that ethoxycarbonyl group optimal substituent effective action benzopyronyl (BTBs), BTB 13a gave an extremely low MIC value 0.002 mM against Staphylococcus aureus 29213, being 3‐fold more active than norfloxacin. Compound exerting most behaviour possessed favourable druggability with no obvious haemolysis, acceptable cytotoxicity propensity induce bacterial resistance. series medicinal chemobiological evaluations disclosed could not only intercalate into DNA produce stable biosupramolecular complexes block replication, form biosupermolecules gyrase, but also disturb cell membrane tempt leakage intracellular contents, fluctuate metabolism oxidative stress, finally resulting in death. Moreover, promising exhibited good vivo efficacy 29213. These results implied large promise members combat

Language: Английский

Citations

0
Design, synthesis and biological evaluation of Meucin-18 derived peptides as efficient broad-spectrum antibacterial agents DOI
Xiaohong Chang, Yang-Chun Ma, Xianghui Zhang

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: 163, P. 108621 - 108621

Published: May 22, 2025

Language: Английский

Citations

0
NIR-II/pH Dual Responsive CuHDB@CaP Nanospheres as a Self-Cascading Catalytic Platform for Highly Efficient Combating Bacterial Infections DOI
Bo Li, Zongchao Jia, Bingyan Li

et al.

ACS Applied Nano Materials, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 28, 2024

The misuse of antibiotics has led to a dramatic increase in bacterial resistance, creating an urgent need for efficient antimicrobial agents with multiple mechanisms action. In this study, Cu was modified berberine derivatives, and core–shell structure successfully developed, resulting light/pH-responsive CuHDB@CaP nanotherapeutic platform. It achieves controlled release CuHDB nanozymes, CaP, which is highly stable neutral or alkaline environments, preventing leakage effectively "switching off" the activity nanozymes. Bacterial metabolism, produces lactic keto acids, lowers pH wound microenvironment. Additionally, exposure 1064 nm near-infrared (NIR) light causes CaP shell collapse, releasing nanozymes on" their enzyme-like activity. This enables platform be both safe efficient. exhibits not only strong photothermal effect but also enhanced glutathione oxidase (GSHOx)-like peroxidase (POD)-like enzyme activities. GSHOx-like contributes generation H2O2, its excellent H2O2 affinity allows it efficiently catalyze conversion sufficient amount •OH through POD-like self-cascading catalytic does require introduction additional promotes consumption GSH infection can kill up 99.0% MRSA AmprE. coli, inhibit biofilm formation without emergence drug exhibit negligible cytotoxicity hemolysis. Treatment experiments mouse models showed that combined NIR could treat infections accelerate healing minimal toxicity normal tissue cells, demonstrating potential clinical treatment skin infections.

Language: Английский

Citations

1