Discovery of Quinazolone Pyridiniums as Potential Broad-Spectrum Antibacterial Agents

Molecules, Год журнала: 2025, Номер 30(2), С. 243 - 243

Опубликована: Янв. 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.

Язык: Английский

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

Future Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Фев. 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

Язык: Английский

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Investigating the Antibacterial Efficiency and Mechanism of Indole- and Naphthalimide-Mediated Benzimidazoles: Membrane Damage, Metabolic Inactivation, and Oxidative Stress against Bacillus subtilis

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 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 series naphthalimide/indole benzimidazoles with diverse amines and aryl rings avoid molecular framework conventional drug molecules overcome cross-resistance issue. Most synthesized compounds, especially electron-withdrawing halide substituents, show broad-spectrum activity against both Gram-positive Gram-negative bacterial strains. Preliminary studies indicate that compounds IB-14 NB-8 display excellent Bacillus subtilis, exceeding performance marketed amoxicillin. In addition rapid bactericidal effect, significantly inhibit formation biofilm, lowering resistance. Moreover, exhibit fast-bactericidal properties, thus shortening time treatment also resisting emergence resistance up 20 passages. Further, biofunctional evaluation reveals effectively disrupt membrane, causing leakage cytoplasmic contents loss in metabolic activity. Both efficiently induce reactive oxygen species (ROS), leading oxidation GSH GSSG, decreasing cell, oxidative damage cells. DNA bind form DNA-IB-14/NB-8 complexes replication protein. The significant binding affinity HSA suggests easy transport candidates target site through carrier These findings suggest multitargeting potential as agents provide possibility global issue multidrug toward antibiotics.

Язык: Английский

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

Bioorganic Chemistry, Год журнала: 2025, Номер 158, С. 108339 - 108339

Опубликована: Март 5, 2025

Язык: Английский

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An efficient synthesis of novel quinolone-thiazolo[3,2-a] pyrimidine hybrid via a facile one-pot, a three-component reaction catalyzed by L-proline as an organo-catalyst

Journal of Sulfur Chemistry, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Март 25, 2025

Язык: 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, Год журнала: 2025, Номер 291, С. 117591 - 117591

Опубликована: Апрель 8, 2025

Язык: Английский

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Synthesis and agricultural antimicrobial evaluation of new quinazoline derivatives containing both a piperazine linker and the N‐acetyl moiety

Pest Management Science, Год журнала: 2024, Номер 80(10), С. 5307 - 5321

Опубликована: Июнь 20, 2024

Abstract BACKGROUND To discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both piperazine linker and the N ‐acetyl moiety were prepared assessed for their antibacterial antifungal activities. RESULTS All target compounds characterized by 1 H 13 C NMR as well high‐resolution mass spectrometry (HRMS), chemical structure most potent compound E19 incorporating 4‐trifluoromethoxy substituent was clearly confirmed via single crystal X‐ray diffraction measurements. The bioassay results indicated that some possessed notable inhibitory effects in vitro against bacterium Xanthomonas oryzae pv. oryzicola ( Xoc ). For example, had an EC 50 (effective concentration 50% activity) value 7.1 μg/mL towards this pathogen, approximately 15‐ 10‐fold effective than commercial bactericides thiodiazole copper bismerthiazol (EC = 110.2 72.4 μg/mL, respectively). Subsequently, mechanistic studies showed likely exerted its efficacies altering cell morphology, increasing permeability bacterial cytoplasmic membrane, suppressing production extracellular polysaccharides enzyme activities (amylase cellulase), blocking swimming motility . Moreover, proteomic analysis revealed could reduce flagellar biosynthesis decrease down‐regulating expression related differential proteins. CONCLUSION Compound exhibited good potential further development bactericide candidate control © 2024 Society Chemical Industry.

Язык: Английский

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In vitro and in vivo evaluation of novel ursolic acid derivatives as potential antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA)

Bioorganic Chemistry, Год журнала: 2024, Номер 154, С. 107986 - 107986

Опубликована: Ноя. 22, 2024

Язык: Английский

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