In vivo efficacy and pharmacological properties of a novel glycopeptide (YV4465) against vancomycin-intermediate Staphylococcus aureus

Yarlagadda, Venkateswarlu; Konai, Mohini M.; Krishnamoorthy, P.; Nimita, Venugopal C.; Shome, Bibek Ranjan; Haldar, Jayanta

doi:10.1016/j.ijantimicag.2015.05.014

Cited by 24 publications

(19 citation statements)

References 14 publications

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“…This compound showed a significant reduction in bacterial titre against VISA in a murine thigh infection model. 92 The compound exhibited improved single-dose pharmacodynamic and pharmacokinetic properties compared to vancomycin. 92 Development of homomeric multivalent analogues.…”

Section: A) Enhanced Binding Affinity To Both the Sensitive And Mutatmentioning

confidence: 99%

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A review on cell wall synthesis inhibitors with an emphasis on glycopeptide antibiotics

et al. 2017

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Cell wall biosynthesis inhibitors (CBIs) have historically been one of the most effective classes of antibiotics. They are the most extensively used class of antibiotics and their importance is exemplified by the β-lactams and glycopeptide antibiotics. However, this class of antibiotics has not received impunity from resistance development. In the wake of this predicament, this review presents the progress of CBIs, especially glycopeptide derivatives as antibiotics to confront antibacterial resistance. The various strategies used for the development of CBIs, their clinical status and possible directions in which this field can evolve have also been discussed.

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Section: A) Enhanced Binding Affinity To Both the Sensitive And Mutatmentioning

confidence: 99%

“…92 The compound exhibited improved single-dose pharmacodynamic and pharmacokinetic properties compared to vancomycin. 92 Development of homomeric multivalent analogues. Glycopeptide antibiotics are known to form dimers through hydrogen bonding and hydrophobic interactions.…”

Section: A) Enhanced Binding Affinity To Both the Sensitive And Mutatmentioning

confidence: 99%

A review on cell wall synthesis inhibitors with an emphasis on glycopeptide antibiotics

et al. 2017

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“…104,105 Nominally, this sugar was designed to produce additional hydrogen bonding interactions with the Lipid II target. 12a was 2-fold more potent than vancomycin against MRSA but 35- and >100-fold more active against VISA and VRE, with an MIC of 2 μg/mL vs both VanA and VanB VRE.…”

Section: New Glycopeptide Derivativesmentioning

confidence: 99%

“…A 100 mg/kg single dose toxicity study in mice was also conducted, with no mortality up to 14 days following administration. 105 The vancosamine has also been alkylated with a positively charged pyridinium group containing a range of alkyl substituents ( 12b–f) . 106 The combination of a lactobiono sugar and positively charged lipophilic moiety significantly improved activity compared to either component alone.…”

Section: New Glycopeptide Derivativesmentioning

confidence: 99%

Developments in Glycopeptide Antibiotics

et al. 2018

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Glycopeptide antibiotics (GPAs) are a key weapon in the fight against drug resistant bacteria, with vancomycin still a mainstream therapy against serious Gram-positive infections more than 50 years after it was first introduced. New, more potent semisynthetic derivatives that have entered the clinic, such as dalbavancin and oritavancin, have superior pharmacokinetic and target engagement profiles that enable successful treatment of vancomycin-resistant infections. In the face of resistance development, with multidrug resistant (MDR) S. pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) together causing 20-fold more infections than all MDR Gram-negative infections combined, further improvements are desirable to ensure the Gram-positive armamentarium is adequately maintained for future generations. A range of modified glycopeptides has been generated in the past decade via total syntheses, semisynthetic modifications of natural products, or biological engineering. Several of these have undergone extensive characterization with demonstrated in vivo efficacy, good PK/PD profiles, and no reported preclinical toxicity; some may be suitable for formal preclinical development. The natural product monobactam, cephalosporin, and β-lactam antibiotics all spawned multiple generations of commercially and clinically successful semisynthetic derivatives. Similarly, next-generation glycopeptides are now technically well positioned to advance to the clinic, if sufficient funding and market support returns to antibiotic development.

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“…Bactericidal and fungicidal time kinetic studies. Bactericidal and fungicidal effects of amphiphiles against S. aureus or C. albicans were determined using previously published protocols (46,47). S. aureus or C. albicans culture was grown until log phase and centrifuged at 5,000 rpm for 10 min.…”

Section: Fig 7 Legend (Continued)mentioning

confidence: 99%

Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms

Gupta

Thakur

Pal

et al. 2019

Antimicrob Agents Chemother

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Interkingdom polymicrobial biofilms formed by Gram-positive Staphylococcus aureus and Candida albicans pose serious threats of chronic systemic infections due to the absence of any common therapeutic target for their elimination. Herein, we present the structure-activity relationship (SAR) of membrane-targeting cholic acid-peptide conjugates (CAPs) against Gram-positive bacterial and fungal strains. Structure-activity investigations validated by mechanistic studies revealed that valine-glycine dipeptide-derived CAP 3 was the most effective broad-spectrum antimicrobial against S. aureus and C. albicans. CAP 3 was able to degrade the preformed single-species and polymicrobial biofilms formed by S. aureus and C. albicans, and CAP 3-coated materials prevented the formation of biofilms. Murine wound and catheter infection models further confirmed the equally potent bactericidal and fungicidal effect of CAP 3 against bacterial, fungal, and polymicrobial infections. Taken together, these results demonstrate that CAPs, as potential broad-spectrum antimicrobials, can effectively clear the frequently encountered polymicrobial infections and can be fine-tuned further for future applications.

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In vivo efficacy and pharmacological properties of a novel glycopeptide (YV4465) against vancomycin-intermediate Staphylococcus aureus

Cited by 24 publications

References 14 publications

A review on cell wall synthesis inhibitors with an emphasis on glycopeptide antibiotics

A review on cell wall synthesis inhibitors with an emphasis on glycopeptide antibiotics

Developments in Glycopeptide Antibiotics

Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms

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