Syntheses and biological evaluation of new cephalosporin-oxazolidinone conjugates

Yan, Suxia; Miller, Marvin J.; Wencewicz, Timothy A.; Möllmann, Ute

doi:10.1039/c0md00015a

Cited by 10 publications

(11 citation statements)

References 28 publications

(14 reference statements)

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“…However, when 2‐aminobenzophenone 1a was reacted with 4‐acetylmorpholine 2g , 3‐acetyl‐2‐oxazolidinone 2h , and 4‐acetylimidazole 2i , 6,12‐diphenyldibenzo[b,f][1,5]diazocine 8a was obtained as the only product with higher yields (34.0, 42.0, and 41.0%, respectively). Morpholine ( 2g ), oxazolidinone ( 2h ), and imidazole ( 2i ) moieties were chosen for applications in biological activity as they are often found in antibacterial drugs, but these results suggest that they inhibit the formation of quinolines.…”

Section: Resultsmentioning

confidence: 99%

Quinolines Formation by Condensation of Heteroaromatic Ketones and 2‐Aminobenzophenones under MW Irradiation

Cho

Song

Lee

et al. 2015

Bulletin Korean Chem Soc

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Section: Resultsmentioning

confidence: 99%

Quinolines Formation by Condensation of Heteroaromatic Ketones and 2‐Aminobenzophenones under MW Irradiation

Cho

Song

Lee

et al. 2015

Bulletin Korean Chem Soc

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“…In general, these β‐lactam antibiotics can inhibit bacterial cell wall synthesis by the inhibition of penicillin‐binding proteins and derange the activity of polymer peptidoglycan biogenesis machinery, which has been deactivated by bacterial beta‐lactamase to open the beta‐lactam ring. Previously, one class of the beta‐lactam antibiotics, cephalosporins/cefazolin, which possesses the core structure, 7‐aminocephalosporanic acid (7‐ACA), has been covalently conjugated with several small molecules to enhance and/or recover their biological activity, including oxazolidinone (at the C3’ position of 7‐ACA), quinolones (at the C3’ position), metallopolymers ( via ionic complexation), siderophore (C7 position substituent), and host defense peptide ( via a cleavable carbamate‐1,4‐triazole linker at the C3’ position) . Interestingly, a report showed that a number of amino acids or dipeptides attached via their C‐terminal carboxylates to the 7‐amino group of 7‐ACA was sufficient to result in significant antibacterial activity when the amino acids or dipeptides alone had none .…”

Section: Introductionmentioning

confidence: 99%

Covalent conjugation of cationic antimicrobial peptides with a β‐lactam antibiotic core

O'Brien-Simpson

Holden

et al. 2018

Peptide Science

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To combat the serious issue of increasing global antibiotic resistance, new antimicrobial therapies are urgently required. As one alternative, previously used antibiotics are being investigated for use in combination with more modern antibiotics including antimicrobial peptides. Towards this goal, 7‐aminocephalosporanic acid, the precursor to the conventional β‐lactam antibiotic, cephalosporin, and the related compound, 7‐aminodesacetoxycephalosporanic acid, were each chemically modified to enable their use in solid phase peptide synthesis for covalent conjugation via their 7‐amino group and a glycolic linker to the N‐terminus of a series of cationic antimicrobial peptides, MSI‐78, CA(1‐7)M(2‐9)NH2 and des‐Chex1‐Arg20. Chemically functionalized Cα‐Fm‐protected 7‐aminocephalosporanic acid and 7‐aminodesacetoxycephalosporanic acid building blocks were separately prepared and attached by their 7‐amino group to the N‐terminus of each peptide on the solid phase via a glutaric anhydride linker. The resulting conjugated AMPs were assessed for antibacterial activity against a panel of six Gram‐negative bacteria, including clinically isolated multi‐drug resistant (MDR) pathogens. Only the conjugated MSI‐78 analogues displayed significant activity against Acinetobacter baumannii and MDR A. baumannii 156 and enhanced activity against Klebsiella pneumoniae. Further work is required to optimize the conjugation of AMPs to 7‐cephalosporanic acid and/or 7‐aminodesacetoxycephalosporanic acid to universally induce an enhanced effect on killing of drug sensitive and MDR bacterial strains that are common causes of hospital‐acquired infections.

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“…reported enhanced antibacterial activity for some cephalosporins with a carbamate derivatization, whereas Yan et al. incorporated a linezolid‐like moiety to obtain cephalosporin–oxazolidinone conjugates . In this respect, we also designed, synthesized and evaluated two β‐lactam carbamates armed with a linezolid‐like molecular fragment.…”

Section: Introductionmentioning

confidence: 99%

Design and Synthesis of 4‐Alkylidene‐β‐lactams: Benzyl‐ and Phenethyl‐carbamates as Key Fragments to Switch on Antibacterial Activity

et al. 2017

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The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2-4 mg L .

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Syntheses and biological evaluation of new cephalosporin-oxazolidinone conjugates

Cited by 10 publications

References 28 publications

Quinolines Formation by Condensation of Heteroaromatic Ketones and 2‐Aminobenzophenones under MW Irradiation

Quinolines Formation by Condensation of Heteroaromatic Ketones and 2‐Aminobenzophenones under MW Irradiation

Covalent conjugation of cationic antimicrobial peptides with a β‐lactam antibiotic core

Design and Synthesis of 4‐Alkylidene‐β‐lactams: Benzyl‐ and Phenethyl‐carbamates as Key Fragments to Switch on Antibacterial Activity

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