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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Cyanomethylquinolones as a New Class of Potential Multitargeting Broad-Spectrum Antibacterial Agents

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(11), P. 9028 - 9053

Published: May 24, 2024

This work identified a class of cyanomethylquinolones (CQs) and their carboxyl analogues as potential multitargeting antibacterial candidates. Most the prepared compounds showed high activities against most tested bacteria, exhibiting lower MIC values (0.125–2 μg/mL) than those clinical norfloxacin, ciprofloxacin, clinafloxacin. The low hemolysis, drug resistance, cytotoxicity, well good predictive pharmacokinetics active CQs revealed development potential. Furthermore, they could eradicate established biofilm, facilitating bacterial exposure to these These induce death through effects, including intercalating into DNA, up-regulating reactive oxygen species, damaging membranes directly, impeding metabolism. Moreover, highly cyclopropyl CQ 15 exhibited more effective in vivo anti-MRSA potency ciprofloxacin. findings highlight broad-spectrum candidates for treating intractable infections.

Language: Английский

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A Unique Hybridization Route to Access Hydrazylnaphthalimidols as Novel Structural Scaffolds of Multitargeting Broad-Spectrum Antifungal Candidates

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(11), P. 8932 - 8961

Published: May 30, 2024

This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential

Language: Английский

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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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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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Discovery of indolylacryloyl-derived oxacins as novel potential broad-spectrum antibacterial candidates

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 270, P. 116392 - 116392

Published: April 1, 2024

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

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

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Anti-biofilm activity of Barleria acanthoides Vahl against Methicillin-resistant Staphylococcus aureus

Current Botany, Journal Year: 2024, Volume and Issue: unknown, P. 157 - 163

Published: Dec. 30, 2024

Methicillin-resistant Staphylococcu aureus (MRSA) biofilms are notoriously difficult to treat due their high resistance antibiotics. This study examines the antibiofilm, antibacterial, and molecular docking potential of Barleria acanthoides ethanol extract against MRSA. A total 18 compounds were identified in GC-MS analysis major beta-asarone (34.09%), Neophytadiene (15.09%) caryophyllene (9.65%). The was very good at killing bacteria; a minimum inhibitory concentration (MIC) 0.5 mg/mL, it stopped MRSA biofilm formation by 80.07%. Molecular studies revealed binding affinities key regulatory proteins LasR SarA, which essential quorum sensing. These findings suggest B. as promising source for developing new therapeutic agents combat biofilm-related infections.

Language: Английский

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