N-Thiolated β-lactams: A new family of anti-Bacillus agents

Turos, Edward; Long, Timothy E.; Heldreth, Bart; Leslie, J. Michelle; Reddy, G. Suresh Kumar; Wang, Yan; Coates, Cristina M.; Konaklieva, Monika I.; Dickey, Sonja; Lim, Daniel V.; Alonso, Eduardo; González, Javier

doi:10.1016/j.bmcl.2006.01.070

Cited by 33 publications

(16 citation statements)

References 8 publications

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“…In addition, ceftobiprole is relatively stable towards class C β -lactamases. The development of new β -lactam antibiotics with alternative mechanisms of action, such as N -alkylthio β -lactams ( Figure 15 ) [105][106][107] , offers an unprecedented new approach to tackle the resistance problem. This family of antibacterial compounds shows promising activity against only a few strategic pathogenic bacteria, a short list that includes MRSA and Bacillus anthracis .…”

Section: Other Approachesmentioning

confidence: 99%

Drug delivery approaches to overcome bacterial resistance to β-lactam antibiotics

Abeylath

Turos

2008

Expert Opinion on Drug Delivery

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Section: Other Approachesmentioning

confidence: 99%

Drug delivery approaches to overcome bacterial resistance to β-lactam antibiotics

Abeylath

Turos

2008

Expert Opinion on Drug Delivery

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“…3-O-acryloyl-1,2-O-isopropylidene-5,6-bis((chlorosuccinyl)oxy)-D-glucofuranose (7) and 6-O-acetyl-3-O-acryloyl-1,2-O-isopropylidene-5-(chlorosuccinyl)oxy-α-D-glucofuranose (10) were both synthesized from 1,2:5,6-di-O-isopropylidine-α-D-glucofuranose-3-acrylate (4) as shown in Scheme 2. Partial deacetonation of 4 with 80% acetic acid at 80°C afforded product 5 in 62% isolated yield.…”

Section: Synthesis Of Acyl Chlorides 7 and 10mentioning

confidence: 99%

Glyconanobiotics: Novel carbohydrated nanoparticle antibiotics for MRSA and Bacillus anthracis

Abeylath

Turos

Dickey

et al. 2008

Bioorganic & Medicinal Chemistry

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This report describes the synthesis and evaluation of glycosylated polyacrylate nanoparticles that have covalently-bound antibiotics within their framework. The requisite glycosylated drug monomers were prepared from one of three known antibiotics, an N-sec-butylthio β-lactam, ciprofloxacin, and a penicillin, by acylation with 3-O-acryloyl-1,2-O-isopropylidene-5,6 bis ((chlorosuccinyl)oxy)-D-glucofuranose (7) or 6-O-acetyl-3-O-acryloyl-1,2-O-isopropylidene-5-(chlorosuccinyl)oxy-α-D-glucofuranose (10). These acrylated monomers were subjected to emulsion polymerization in a 7:3 (w:w) mixture of butyl acrylate-styrene in the presence of sodium dodecyl sulfate as surfactant (3 weight %) and potassium persulfate as a radical initiator (1 weight %). The resulting nanoparticle emulsions were characterized by dynamic light scattering and found to have similar diameters (~40 nm) and size distributions to those of our previously studied systems. Microbiological testing showed that the N-sec-butylthio β-lactam and ciprofloxacin nanoparticles both have powerful in vitro activities against methicillin-resistant Staphylococcus aureus and Bacillus anthracis, while the penicillin-bound nanoparticles have no antimicrobial activity. This indicates the need for matching a suitable antibiotic with the nanoparticle carrier. Overall, the study shows that even relatively large, polar acrylate monomers (MW>1000 amu) can be efficiently incorporated into the nanoparticle matrix by emulsion polymerization, providing opportunities for further advances in nanomedicine.

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“…Furthermore, additional C3 methyl substitution led to increased activity. All together, the two most potent compounds from the library of 100 N1‐thio‐substituted monocyclic β‐lactams were compounds 116 and 117 , showing MIC values as low as 0.5 μg/mL, as presented in Table …”

Section: N1‐thio‐substituted Monocyclic β‐Lactamsmentioning

confidence: 98%

“…All together, the two most potent compounds from the library of 100 N1-thio-substituted monocyclic β-lactams were compounds 116 and 117, showing MIC values as low as 0.5 μg/mL, as presented in Table XII. 158,159 In further work, a library of oxidized N1-thio-substituted monocyclic β-lactams was prepared, to which many derivatives were contributed by Jarrahpour et al 160,161 N1-sulfinyl, N1-sulfonyl, and N1-sulfonate derivatives were observed to be inactive in an antibacterial assay on MRSA, Bacillus and Pseudomonas strains, with the exception of compound 118, displaying activity against P. aeruginosa, B. subtilis, and S. aureus with respective MIC values of 8, 2, and 4 μg/mL (Fig. 30).…”

Section: N1-thio-substituted Monocyclic β-Lactamsmentioning

confidence: 99%

Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

Decuyper

Jukič

Sosič

et al. 2017

Medicinal Research Reviews

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Due to the widespread emergence of resistant bacterial strains, an urgent need for the development of new antibacterial agents with novel modes of action has emerged. The discovery of naturally occurring monocyclic β-lactams in the late 1970s, mainly active against aerobic Gram-negative bacteria, has introduced a new approach in the design and development of novel antibacterial β-lactam agents. The main goal was the derivatization of the azetidin-2-one core in order to improve their antibacterial potency, broaden their spectrum of activity, and enhance their β-lactamase stability. In that respect, our review covers the updates in the field of monocyclic β-lactam antibiotics during the last three decades, taking into account an extensive collection of references. An overview of the relationships between the structural features of these monocyclic β-lactams, classified according to their N-substituent, and the associated antibacterial or β-lactamase inhibitory activities is provided. The different paragraphs disclose a number of well-established classes of compounds, such as monobactams, monosulfactams, monocarbams, monophosphams, nocardicins, as well as other known representative classes. Moreover, this review draws attention to some less common but, nevertheless, possibly important types of monocyclic β-lactams and concludes by highlighting the recent developments on siderophore-conjugated classes of monocyclic β-lactams.

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N-Thiolated β-lactams: A new family of anti-Bacillus agents

Cited by 33 publications

References 8 publications

Drug delivery approaches to overcome bacterial resistance to β-lactam antibiotics

Drug delivery approaches to overcome bacterial resistance to β-lactam antibiotics

Glyconanobiotics: Novel carbohydrated nanoparticle antibiotics for MRSA and Bacillus anthracis

Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

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