Macrolides

Arsić, Biljana; Novak, Predrag; Kragol, Goran; Barber, Jill; Rimoli, Maria Grazia; Sodano, Federica

doi:10.1515/9783110515756

Cited by 9 publications

(4 citation statements)

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“…The first chemical modulation to access the ketolides used in therapy, was to eliminate L-cladinose in C3 by a ketone function. Indeed, the presence of this sugar is not necessary to induce a notable antibacterial activity [99]. The suppression of L-cladinose has thus made it possible to improve the stability in acid medium of ketolides, to widen their spectrum of antibacterial action towards Gram-positive germs including the strains resistant to other macrolides and to avoid induction MLSB resistance as well as the efflux of the antibiotic [100] [101] [102] [103].…”

Section: Access To the First Ketolides: Telithromycin And Cethromycinmentioning

confidence: 99%

Pharmacochemical Aspects of the Evolution from Erythromycin to Neomacrolides, Ketolides and Neoketolides

Ouattara¹,

Songuigama²,

Jean-Paul³

2020

OJMC

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Antibiotic macrolides are experiencing renewed interest in anti-infective therapy since the advent of ketolides. This therapeutic class was introduced in order to broaden the narrow antibacterial spectrum of macrolides and to cope with the emergence of germs resistant to Erythromycin A and its hemisynthetic derivatives or neomacrolides (Clarithromycin, Roxithromycin, Azithromycin, Dirithromycin). From a pharmacochemical point of view, ketolides were first of all obtained by operating chemical modulations on Erythromycin A to obtain the neomacrolides, then, by replacing the neutral sugar (L-cladinose) in C3 by a ketone function coupled with the creation of an oxazolidinone like heterocycle in C11 and C12 in place of the hydroxyls present in these positions (Telithromycin, Cethromycin, Solithromycin). These modulations have enabled the improvement of the chemical stability of ketolides in gastric acid medium and increase their affinity for the ribosomal target, hence the broadening of their spectrum of action towards Gram positive germs including strains resistant to other macrolides and to neomacrolides. Therefore, the objective of this systematic review is to report the various pharmacochemical aspects undertaken since 1952 in the macrolide series based on the structure of Erythromycin A. These aspects will focus on the pharmacomodulations that have led, year after year, to the optimization of stability, the improvement of the pharmacodynamic and pharmacokinetic profile and that have allowed the development of neomacrolides, ketolides and neoketolides, which are today essential in the management of severe bronchopulmonary infections.

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Section: Access To the First Ketolides: Telithromycin And Cethromycinmentioning

confidence: 99%

Pharmacochemical Aspects of the Evolution from Erythromycin to Neomacrolides, Ketolides and Neoketolides

Ouattara¹,

Songuigama²,

Jean-Paul³

2020

OJMC

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“…Macrolide antibiotics have been proven as effective, anti-bacterial agents [ 1 ], some active against both Gram-positive and Gram-negative bacteria. However, searching for macrolides active against Gram-negative bacteria is a difficult task and is not a systematic process.…”

Section: Introductionmentioning

confidence: 99%

Computational Studies on Selected Macrolides Active against Escherichia coli Combined with the NMR Study of Tylosin A in Deuterated Chloroform

et al. 2022

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Although many antibiotics are active against Gram-positive bacteria, fewer also show activity against Gram-negative bacteria. Here, we present a combination of in silico (electron ion-interaction potential, molecular docking, ADMET), NMR, and microbiological investigations of selected macrolides (14-membered, 15-membered, and 16-membered), aiming to discover the pattern of design for macrolides active against Gram-negative bacteria. Although the conformational studies of 14-membered and 15-membered macrolides are abundant in the literature, 16-membered macrolides, and their most prominent representative tylosin A, have received relatively little research attention. We therefore report the complete 1H and 13C NMR assignment of tylosin A in deuterated chloroform, as well as its 3D solution structure determined through molecular modelling (conformational search) and 2D ROESY NMR. Additionally, due to the degradation of tylosin A in deuterated chloroform, other species were also detected in 1D and 2D NMR spectra. We additionally studied the anti-bacterial activity of tylosin A and B against selected Gram-positive and Gram-negative bacteria.

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“…A well-known class of antibacterials, 14- and 15-membered macrolides are widely prescribed to treat upper and lower respiratory tract infections [ 1 ]. Azithromycin is a semisynthetic 15-membered macrolide antibiotic derived from erythromycin, possessing a broad spectrum of antibacterial potency and favorable pharmacokinetics [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Screening of Novel Antimicrobial Diastereomers of Azithromycin–Thiosemicarbazone Conjugates: A Combined LC-SPE/Cryo NMR, MS/MS and Molecular Modeling Approach

et al. 2022

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A well-known class of antibacterials, 14- and 15-membered macrolides are widely prescribed to treat upper and lower respiratory tract infections. Azithromycin is a 15-membered macrolide antibiotic possessing a broad spectrum of antibacterial potency and favorable pharmacokinetics. Bacterial resistance to marketed antibiotics is growing rapidly and represents one of the major global hazards to human health. Today, there is a high need for discovery of new anti-infective agents to combat resistance. Recently discovered conjugates of azithromycin and thiosemicarbazones, the macrozones, represent one such class that exhibits promising activities against resistant pathogens. In this paper, we employed an approach which combined LC-SPE/cryo NMR, MS/MS and molecular modeling for rapid separation, identification and characterization of bioactive macrozones and their diastereomers. Multitrapping of the chromatographic peaks on SPE cartridges enabled sufficient sample quantities for structure elucidation and biological testing. Furthermore, two-dimensional NOESY NMR data and molecular dynamics simulations revealed stereogenic centers with inversion of chirality. Differences in biological activities among diastereomers were detected. These results should be considered in the process of designing new macrolide compounds with bioactivity. We have shown that this methodology can be used for a fast screening and identification of the macrolide reaction components, including stereoisomers, which can serve as a source of new antibacterials.

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Macrolides

Cited by 9 publications

References 0 publications

Pharmacochemical Aspects of the Evolution from Erythromycin to Neomacrolides, Ketolides and Neoketolides

Pharmacochemical Aspects of the Evolution from Erythromycin to Neomacrolides, Ketolides and Neoketolides

Computational Studies on Selected Macrolides Active against Escherichia coli Combined with the NMR Study of Tylosin A in Deuterated Chloroform

Screening of Novel Antimicrobial Diastereomers of Azithromycin–Thiosemicarbazone Conjugates: A Combined LC-SPE/Cryo NMR, MS/MS and Molecular Modeling Approach

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