Synthesis and antibacterial medicinal evaluation of carbothioamido hydrazonyl thiazolylquinolone with multitargeting antimicrobial potential to combat increasingly global resistance

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 275, P. 116626 - 116626

Published: June 27, 2024

Language: Английский

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Discovery of Quinazolone Pyridiniums as Potential Broad-Spectrum Antibacterial Agents

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

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A comprehensive insight into naphthalimides as novel structural skeleton of multitargeting promising antibiotics

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 16

Published: Feb. 16, 2025

The globally growing antimicrobial resistance seriously threatens human health, increasing efforts have been devoting to the development of novel antibiotics. Naphthalimides contain a special skeleton cyclic double imides and naphthalene framework, this unique structure can exert multitargeting abilities which are helpful overcome escalating issue resistance. Therefore, research in connection with naphthalimides as agents is becoming progressively active. It has revealed that structural promising antibiotics could not only target DNAs enzymes, disturb membrane, produce reactive oxygen species, etc. suggesting actions do induce resistance, but also show broad spectrum safety profile pharmacokinetic characteristics, implying large potential new type via continuous toward naphthalimides. This review presents discusses rational design strategies, structure-activity relationships, mechanisms action, comprehensive view providing insight for efficient, broad-spectrum, low-toxic naphthalimide

Language: Английский

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Benzo-α-pyrone-derived multitargeting actions to enhance the antibacterial performance of sulfanilamides against Escherichia coli

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

Published: March 5, 2025

Language: Английский

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Unlocking the Antibacterial Potential of Naphthalimide–Coumarins to Overcome Drug Resistance with Antibiofilm and Membrane Disruption Ability against Escherichia coli

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Resistance by bacteria to available antibiotics is a threat human health, which demands the development of new antibacterial agents. Considering prevailing conditions, we have developed library naphthalimide-coumarin moieties as broad-spectrum agents fight against awful drug resistance. Preliminary studies indicate that compounds

Language: Английский

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Theragnostic Dual‐Action Platform: Ruthenium p‐Cymene‐Derived Metalloantibiotics With NIR‐II Photoacoustic Spectral Signal

Small, Journal Year: 2025, Volume and Issue: unknown

Published: May 15, 2025

Abstract This study initiates the development of Ru1, a metalloantibiotic derived from p ‐cymene, which delivers dual functionality. Our approach begins with design and synthesis half‐sandwich ruthenium complexes, Ru1‐Ru11. By varying structure ancillary ligand, biological activities eleven complexes against five bacterial strains were explored. Most active, Ru1 (4 µg mL −1 ) Ru 11 (1 mL−1) was solicited for further study. To assess safety these compounds, hemolytic activity cytotoxicity evaluated human red blood cells (RBCs) HEK cell line, respectively. Based on results, selected investigation. exhibited significant efficacy MRSA (methicillin‐resistant S. aureus VRSA (vancomycin‐resistant ). Additionally, strong DNA‐binding affinity (K b = 1.73*10 5 M 1.6 *10 Molecular docking studies highlighted Ru1's potent interaction active sites key proteins, including MurB, topoisomerase II DNA gyrase, 1BNA, binding energies −12.05 kcal/mol, −6.30 kcal/mol −7.77 Furthermore, showed high photoacoustic signal intensity at 902 nm in MSOT imaging, underscoring its potential as dual‐function therapeutic diagnostic (theragnostic) agent.

Language: Английский

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Self-Assembling Nucleopeptides Exhibiting Strong Antimicrobial Activity against Multidrug-Resistant Clinically Isolated Strains and In Vitro Wound Healing Compatibility

ACS Applied Bio Materials, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

To combat the emerging threat of antimicrobial resistance (AMR), in this study, two amphiphilic nucleopeptides (NPs) were synthesized by conjugating nucleobase thymine with peptide amphiphiles. These compounds fully characterized using various analytical techniques. Notably, both formed hydrogels milli-Q water at neutral pH (pH 6.9). X-ray diffraction further confirmed antiparallel β-sheet-like structures, along aromatic π–π stacking and hydrogen-bonding (H-bonding) interactions between moieties gel phase. Field emission gun transmission electron microscopy revealed a nanofibrillar network structure these self-assembled peptides. A significant feature supramolecular self-assemblies is their potent activity against types bacteria, such as Gram-positive Gram-negative standard American Type Culture Collection (ATCC) including Bacillus subtilis, Escherichia coli, multidrug-resistant clinically isolated ATCC strains methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Pseudomonas aeruginosa. Among these, peptides demonstrated remarkable inhibition MRSA (MIC: 15.92–16.86 μM) K. pneumoniae 8.8–50 μM), highlighting potential agents deadly (MDR) bacteria. Additionally, assemblies found to be highly biocompatible, MTT assays on HEK-293 cells, showing IC50 values range 0.5–1.1 mM. In an vitro wound healing assay HeLa fluorescence that treatment did not disrupt cell or mitochondrial membranes cells. This work presents broad-spectrum efficacy MDR demonstrates high biocompatibility, supporting use agents.

Language: Английский

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

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

Published: April 8, 2025

Language: Английский

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Identification of CH2-linker modified desfluoroquinolone-aminopyrimidine hybrids to combat antibiotic-resistant gram-positive bacteria

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

Published: April 21, 2025

Language: Английский

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

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

Published: April 1, 2025

Language: Английский

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