Structure-based design of bacterial transglycosylase inhibitors incorporating biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties

Yu, Jui-Yin; Cheng, Hsiu-Jung; Wu, Huei-Ru; Wu, Wen‐Teng; Lu, J.G.; Cheng, Ting‐Jen R.; Fang, Jim‐Min

doi:10.1016/j.ejmech.2018.03.034

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…A set of hybrid compounds tethered to different fragments, which were 1,2,3-triazole, biphenyl, 2-alkoxy-3-phosphorylpropanoate, and an amine linker were synthesised and tested for bacterial transglycosylase inhibitory potency against Acinetobacter baumannii. 92 The transglycosylase inhibitory activities of the synthesised samples were lower at 500 µM than those of compounds 55-57 ( Fig. 7), which showed much higher transglycosylase inhibitory activity (99% for each sample) at 200 µM.…”

Section: Antimicrobial Activitymentioning

confidence: 87%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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Section: Antimicrobial Activitymentioning

confidence: 87%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

614

289

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“…Therefore, several studies have been initiated to construct Mm analogs with improved pharmacokinetics employing both chemoenzymatic and genetic engineering techniques [15]. Numerous derivatives with altered biological activities were created, using the active Mm pharmacophore as a starting point [55][56][57][58]. Taking into account that chemical synthesis of Mm is challenging [59], the production of novel Mm derivatives through fermentation and/or chemoenzymatic approaches would be highly desirable.…”

Section: Discussionmentioning

confidence: 99%

Genetic Engineering of Streptomyces ghanaensis ATCC14672 for Improved Production of Moenomycins

2021

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Streptomycetes are soil-dwelling multicellular microorganisms famous for their unprecedented ability to synthesize numerous bioactive natural products (NPs). In addition to their rich arsenal of secondary metabolites, Streptomyces are characterized by complex morphological differentiation. Mostly, industrial production of NPs is done by submerged fermentation, where streptomycetes grow as a vegetative mycelium forming pellets. Often, suboptimal growth peculiarities are the major bottleneck for industrial exploitation. In this work, we employed genetic engineering approaches to improve the production of moenomycins (Mm) in Streptomyces ghanaensis, the only known natural direct inhibitors of bacterial peptidoglycan glycosyltransferses. We showed that in vivo elimination of binding sites for the pleiotropic regulator AdpA in the oriC region strongly influences growth and positively correlates with Mm accumulation. Additionally, a marker- and “scar”-less deletion of moeH5, encoding an amidotransferase from the Mm gene cluster, significantly narrows down the Mm production spectrum. Strikingly, antibiotic titers were strongly enhanced by the elimination of the pleiotropic regulatory gene wblA, involved in the late steps of morphogenesis. Altogether, we generated Mm overproducers with optimized growth parameters, which are useful for further genome engineering and chemoenzymatic generation of novel Mm derivatives. Analogously, such a scheme can be applied to other Streptomyces spp.

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“…Fang's group constructed a library of moenomycin mimics comprising biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties. 120 The biphenyl moiety as a surrogate of disaccharide to mimic the transition state of transglycosylation, which involves an oxocarbenium ion of relatively flat half-chair conformation. The phosphorylpropanoate group is an alternative to the phosphoglycerate moiety in moenomycin, offering improved stability.…”

Section: Potential Transglycosylase Inhibitorsmentioning

confidence: 99%

Advances and prospects of analytic methods for bacterial transglycosylation and inhibitor discovery

Hsu,

Fang

2024

Analyst

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Structure-based design of bacterial transglycosylase inhibitors incorporating biphenyl, amine linker and 2-alkoxy-3-phosphorylpropanoate moieties

Cited by 6 publications

References 49 publications

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Genetic Engineering of Streptomyces ghanaensis ATCC14672 for Improved Production of Moenomycins

Advances and prospects of analytic methods for bacterial transglycosylation and inhibitor discovery

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