Synthesis and antibacterial activity against Clostridium difficile of novel demethylvancomycin derivatives

Zhang, Si-Ji; Yang, Qing; Xu, Li; Chang, Jun

doi:10.1016/j.bmcl.2012.06.039

Cited by 14 publications

(14 citation statements)

References 27 publications

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“…In 2012, a series of 17 novel N -substituted demethylvancomycin derivatives were synthesized and evaluated in vitro against C. difficile by Zhang et al [199]. Structurally, demethylvancomycin differs from VAN by the replacement of a methyl group by a hydrogen atom of the N -terminal amino group and it demonstrated similar activity as VAN against Gram-positive pathogens [200].…”

Section: Newer Agents For CDImentioning

confidence: 99%

“…Structurally, demethylvancomycin differs from VAN by the replacement of a methyl group by a hydrogen atom of the N -terminal amino group and it demonstrated similar activity as VAN against Gram-positive pathogens [200]. Another structural modification of this glycopeptide is the introduction of a lipophilic side chain on the NH 2 group of the amino sugar moiety such as in telavancin, oritavancin, and dalbavancin [199]. These aforementioned agents have been reported to show greater activity against C. difficile than VAN [201, 202].…”

Section: Newer Agents For CDImentioning

confidence: 99%

“…Based on these observations, a focused chemical library of semisynthetic demethylvancomycin derivatives bearing N -substituted arylmethylene and aliphatic motifs was synthesized and tested. Biological evaluation revealed that three N -substituted arylmethylene derivatives with structural similarity to oritavancin demonstrated more potent activity against four C. difficile strains than VAN or demethylvancomycin with MICs of 0.25, 0.125-0.25, and 0.25-0.5 µg/mL, respectively [199]. This class of glycopeptide antibiotics interacts with the bacterial membrane, dissipates membrane potential, and inhibits peptidoglycan biosynthesis [203].…”

Section: Newer Agents For CDImentioning

confidence: 99%

“…Derivatives with heterocyclic ring motifs had higher MICs against the ATCC 43255 strain (0.5-1 µg/mL) while fused aromatic analogs exhibited lower MICs (0.25 µg/mL). In general, the aliphatic derivatives of demethylvancomycin did not exhibit significant activity against C. difficile and the antibacterial activity was inversely related to side chain length [199]. …”

Section: Newer Agents For CDImentioning

confidence: 99%

See 3 more Smart Citations

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Tsutsumi¹,

Owusu²,

Hurdle³

et al. 2013

CTMC

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Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance.

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Section: Newer Agents For CDImentioning

confidence: 99%

Section: Newer Agents For CDImentioning

confidence: 99%

Section: Newer Agents For CDImentioning

confidence: 99%

Section: Newer Agents For CDImentioning

confidence: 99%

See 2 more Smart Citations

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Tsutsumi¹,

Owusu²,

Hurdle³

et al. 2013

CTMC

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show abstract

“…We recently reported the synthesis of seventeen novel N‐substituted ( N ‐arylmethylene or ‐aliphatic substituents) demethylvancomycin derivatives and their antibacterial activities against Clostridium difficile 14. It was found that several compounds with N ‐arylmethylene substituents, structurally similar to oritavancin, showed more potent antibacterial activity against C. difficile than vancomycin ( 1 ) or demethylvancomycin ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Olfactory Properties of Silicon‐Containing Analogs of Rosamusk, Romandolide, and Applelide: Insights into the Structural Parameters of Linear Alicyclic Musks

Liu

Zou

et al. 2016

Eur J Org Chem

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A series of silicon-containing derivatives of linear alicyclic musks comprising sila-Rosamusk (3b), sila-Romandolide (5b), sila-Applelide (11b), and the corresponding dehydro derivatives was synthesized from sila-analogs of Artemone and Herbac, respectively, by means of sodium borohydride reduction and subsequent esterification with the corresponding acid chlorides in the presence of triethylamine. The olfactory properties of the new sila-odorants 3b-13b are reported in compari-

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Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug‐Resistant Bacteria

et al. 2013

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Five novel N-substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure-based approach. The in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), gentamicin-resistant Enterococcus faecalis (GRE), methicillin-resistant Streptococcus pneumoniae (MRS), and vancomycin-resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N-(6-phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ~18-fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half-life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.

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Synthesis and antibacterial activity against Clostridium difficile of novel demethylvancomycin derivatives

Cited by 14 publications

References 27 publications

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

Synthesis and Olfactory Properties of Silicon‐Containing Analogs of Rosamusk, Romandolide, and Applelide: Insights into the Structural Parameters of Linear Alicyclic Musks

Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug‐Resistant Bacteria

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