A Review of Antibacterial Candidates with New Modes of Action

ACS Infectious Diseases, Journal Year: 2024, Volume and Issue: 10(10), P. 3440 - 3474

Published: July 17, 2024

There is a lack of new antibiotics to combat drug-resistant bacterial infections that increasingly threaten global health. The current pipeline clinical-stage antimicrobials primarily populated by "new and improved" versions existing antibiotic classes, supplemented several novel chemical scaffolds act on traditional targets. fresh chemotypes acting previously unexploited targets (the "holy grail" for due their scarcity) particularly unfortunate as these offer the greatest opportunity innovative breakthroughs overcome resistance. In recognition potential, this review focuses subset high value antibiotics, providing structures where available. This candidates have progressed clinical trials, well selected examples promising pioneering approaches in advanced stages development, order stimulate additional research aimed at combating infections.

Language: Английский

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Targeting Acinetobacter baumannii resistance-nodulation-division efflux pump transcriptional regulators to combat antimicrobial resistance

npj Antimicrobials and Resistance, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 25, 2025

Regulatory elements controlling gene expression fine-tune bacterial responses to environmental cues, including antimicrobials, optimize survival. Acinetobacter baumannii, a pathogen notorious for antimicrobial resistance, relies on efficient efflux systems. Though the role of systems in antibiotic expulsion are well recognized, regulatory mechanisms their remain understudied. This review explores current understanding these regulators, aiming inspire strategies combat resistance and improve therapeutic outcomes.

Language: Английский

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Lasso peptides sviceucin and siamycin I have anti-virulence activity and restore vancomycin effectiveness in vancomycin-resistant pathogens

iScience, Journal Year: 2025, Volume and Issue: 28(3), P. 111922 - 111922

Published: Jan. 30, 2025

Language: Английский

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Green decontaminants for the remediation of chemical, biological, radiological and nuclear contaminants

Phytochemistry Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Language: Английский

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Fe(II)-Photoantibiotics for Potential Antibacterial, Antibiofilm, and Infective Wound Healing Applications in Rat Model

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

Published: Feb. 6, 2025

Herein, five Fe(II) complexes, viz., [Fe(N,N,N)2](ClO4)2, where N,N,N = 4′-phenyl-2,2′:6′,2″-terpyridine (Ph-tpy, Fe1), 4′-(4 aminophenyl) 2,2′:6′,2″ terpyridine (NH2-Phtpy, Fe2), 4-([2,2′:6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline (NMe2-Phtpy, Fe3), 4′-(p-nitrophenyl)-2.2′:6′,2″-terpyridine (NO2-Phtpy, Fe4), and 4′-(4-trifluoromethylphenyl)-2,2':6′,2′′-terpyridine (CF3-Phtpy, Fe5) were developed screened for their visible-light-triggered antibacterial activity. Fe1–Fe5 exhibited absorption at ca. 450–600 nm, beneficial photodynamic therapy (aPDT) under visible light exposure. The excellent photostability ideal energy gap between T1 S0 of the complexes made them good photosensitizers aPDT. Fe5 had best activity against Escherichia coli Bacillus subtilis upon exposure to 400–700 nm (10 J cm–2) due reactive oxygen species (ROS) generation. Further, showed antibiofilm on different medical-grade biomaterials devices. Biocompatibility was validated using in vivo chicken embryonic models (in ovo). Moreover, studies that efficiently healed infected wounds within 9 days.

Language: Английский

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Short Synthesis of Structurally Diverse N-Acylhomoserine Lactone Analogs and Discovery of Novel Quorum Quenchers Against Gram-Negative Pathogens

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1775 - 1775

Published: Feb. 19, 2025

Quorum quenchers are emerging as an alternative to conventional antimicrobials, since they hinder the development of virulence or resistance mechanisms but without killing microorganisms, thus, reducing risk antimicrobial resistance. Many quorum analogs natural quorum-sensing signaling molecules autoinducers. Thus, different N-acylhomoserine lactones (AHLs) have been reported for controlling production biofilms in Gram-negative pathogens. Herein we report preparation AHL with a variety N-substituents just two steps from readily available N-substituted hydroxyproline esters. The substrates underwent oxidative radical scission pyrrolidine ring. resulting β-aminoaldehyde reduction and situ cyclization give homoserine lactones, N- N,N-substituted amino derivatives high optical purity. libraries were screened inhibition violacein Chromobacterium violaceum, pathogen. For first time, N,N-disubstituted studied. Several N-sulfonyl derivatives, one carbamoyl, N-alkyl-N-sulfonyl lactone displayed promising inhibitory activity. Moreover, did not display microbicide action against S. aureus, C. jejuni, enterica, P. aeruginosa, albicans, confirming pure QQ determination structure–activity relationships silico ADME studies also reported, which valuable design next generations agents.

Language: Английский

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PaAP-Activatable NIR Probe for Diagnosing, Imaging, and Discovering Small-Molecule Therapeutics against Implant-Associated Biofilm Infections

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

Published: March 26, 2025

Biofilm formation on medical implants causes implant-associated infections (IAIs), leading to high morbidity and mortality. Developing molecular tools for precise biofilm detection, along with novel strategies agents target biofilm-related IAIs, is crucial improving treatment options patient outcomes. Pseudomonas aeruginosa aminopeptidase (PaAP), a key biofilm-associated virulence factor, promising combating infections. Here, we developed PaAP-activatable near-infrared (NIR) fluorescent probe, Hcy-NEO-Leu, real-time, specific, sensitive detection of PaAP activity. This probe enables noninvasive imaging the P. in vitro vivo. The also identified LY-58, lycorine derivative that disrupts without affecting bacterial growth or mammalian cell viability, enhancing tobramycin penetration overcoming antibiotic resistance. study introduces LY-58 as adjunctive therapy. In conclusion, NIR combined offers innovative early diagnosis effective IAIs.

Language: Английский

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The antimycotic 5-fluorocytosine is a virulence inhibitor of uropathogenic Escherichia coli and eradicates biofilm-embedded bacteria synergizing with β-lactams

Antimicrobial Agents and Chemotherapy, Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Biofilm can enhance antibiotic tolerance in bacteria, making treatment of biofilm-associated infections clinical settings a significant challenge. 5-Fluorocytosine (5-FC), an FDA-approved drug mostly used as antifungal, hinder biofilm formation and production virulence factors Gram-negative bacteria. In this study, we tested 5-FC on nine uropathogenic Escherichia coli (UPEC) strains plus fecal isolate. Our data indicated that reduced curli fiber gene expression inhibited UPEC strains. Unlike what was observed other microorganisms, antivirulence antibiofilm properties were unaffected by either growth temperature or the medium pH, which might prove critical urinary tract infection (UTI) treatment. Additionally, impaired various factors, including secreted toxins type I P fimbriae, thus leading to decreased adherence bladder epithelial cells improved survival host cells. Finally, found combination with β-lactams, but not classes antibiotics, significantly lowered viability bacteria preformed biofilms. Despite small set pathogenic E. vitro model, our findings strongly suggest be possible candidate agent, particularly synergistic approach β-lactam antibiotics.

Language: Английский

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Quorum sensing inhibitors (QSIs): a patent review (2019-2023)

Expert Opinion on Therapeutic Patents, Journal Year: 2025, Volume and Issue: unknown

Published: April 12, 2025

The collective behavior of bacteria is regulated by Quorum Sensing (QS), in which release chemical signals and express virulence genes a cell density-dependent manner. inhibitors (QSIs) are large class natural synthetic compounds that have the potential to competitively inhibit (QS) systems several pathogens blocking their mechanisms. They considered promising deal with antimicrobial resistance, providing an opportunity develop new drugs against these targets. present review represents comprehensive analysis patents patent applications available on Espacenet Google Patent, from 2019 2023 referring therapeutic use inhibitors. Unlike classical antibiotics, target basic cellular metabolic processes, QSIs provide alternative attenuating pathogenicity without putting selective pressure bacteria. general belief pose no or little since do not affect growth. To date, seen as most traditional antibiotics. next big step this area research its succession clinical stage.

Language: Английский

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Emerging antibiotic resistance by various novel proteins/enzymes

European Journal of Clinical Microbiology & Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 15, 2025

Language: Английский

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