Dithiocarbamates combined with copper for revitalizing meropenem efficacy against NDM-1-producing Carbapenem-resistant Enterobacteriaceae

Chen, Cheng; Yang, Ke‐Wu; Zhai, Le; Ding, Huan‐Huan; Chigan, Jia-Zhu

doi:10.1016/j.bioorg.2021.105474

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…Isothermal titration calorimetry (ITC) measurements were performed as described previously ( Zhang et al, 2018 ; Chen et al, 2022 ). OXA-48, imipenem, and quercetin were prepared in 30 mM Tris, 5 mM NaHCO 3 (pH 7.5) supplemented with 5% DMSO.…”

Section: Methodsmentioning

confidence: 99%

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Discovery of Quercetin and Its Analogs as Potent OXA-48 Beta-Lactamase Inhibitors

Zhang

Chen²,

Cheng³

et al. 2022

Front. Pharmacol.

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Carbapenem resistance in Enterobacteriaceae caused by OXA-48 β-lactamase is a growing global health threat and has rapidly spread in many regions of the world. Developing inhibitors is a promising way to overcome antibiotic resistance. However, there are few options for problematic OXA-48. Here we identified quercetin, fisetin, luteolin, 3′,4′,7-trihydroxyflavone, apigenin, kaempferol, and taxifolin as potent inhibitors of OXA-48 with IC50 values ranging from 0.47 to 4.54 μM. Notably, the structure-activity relationship revealed that the substitute hydroxyl groups in the A and B rings of quercetin and its structural analogs improved the inhibitory effect against OXA-48. Mechanism studies including enzymatic kinetic assay, isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR) analysis demonstrated that quercetin reversibly inhibited OXA-48 through a noncompetitive mode. Molecular docking suggested that hydroxyl groups at the 3′, 4′ and 7 positions in flavonoids formed hydrogen-bonding interactions with the side chains of Thr209, Ala194, and Gln193 in OXA-48. Quercetin, fisetin, luteolin, and 3′,4′,7-trihydroxyflavone effectively restored the antibacterial efficacy of piperacillin or imipenem against E. coli producing OXA-48, resulting in 2–8-fold reduction in MIC. Moreover, quercetin combined with piperacillin showed antimicrobial efficacy in mice infection model. These studies provide potential lead compounds for the development of β-lactamase inhibitors and in combination with β-lactams to combat OXA-48 producing pathogen.

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Section: Methodsmentioning

confidence: 99%

“…The mouse systemic infection model was developed as previously reported ( King et al, 2014 ; Chen et al, 2022 ). E. coli BW25113 ∆ acrA ∆ bamB (OXA-48) were cultured to an OD 600 value of 1.0 and then washed with PBS three times.…”

Section: Methodsmentioning

confidence: 99%

Discovery of Quercetin and Its Analogs as Potent OXA-48 Beta-Lactamase Inhibitors

Zhang

Chen²,

Cheng³

et al. 2022

Front. Pharmacol.

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“…Given that both thydroxamates and thiosemicarbazones were reported to have anticancer efficacy [50] , [51] , [52] , [53] , we performed toxicity assay and fluorescence microscopy images of the human breast cancer cells (MCF-7) treated with these compounds (see supporting information) [54,55]. As shown in Fig.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Hydroxamate and thiosemicarbazone: Two highly promising scaffolds for the development of SARS-CoV-2 antivirals

Chigan

et al. 2022

Bioorganic Chemistry

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“…Indisputably, discovering highly efficient remedies for these infectious diseases has exponentially emerged as an area of focus [ 9 , 10 , 11 ]. In this context, the synthesis of various dithiocarbamates (DTCs), which revealed remarkable properties and diverse applications in bioorganic and medicinal chemistry such as fungicides and pesticides, crop protection agents and anticancer agents, is thoroughly crucial [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. For example, take Zineb, Maneb and disulfiram as imperative dithiocarbamate-based biologically active molecules ( Figure 1 ) [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of novel antibacterial and antifungal dithiocarbamate-containing piperazine derivatives via re-engineering multicomponent approach

Halimehjani

Dehghan

Tafakori

et al. 2022

Heliyon

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Dithiocarbamates combined with copper for revitalizing meropenem efficacy against NDM-1-producing Carbapenem-resistant Enterobacteriaceae

Cited by 11 publications

References 52 publications

Discovery of Quercetin and Its Analogs as Potent OXA-48 Beta-Lactamase Inhibitors

Discovery of Quercetin and Its Analogs as Potent OXA-48 Beta-Lactamase Inhibitors

Hydroxamate and thiosemicarbazone: Two highly promising scaffolds for the development of SARS-CoV-2 antivirals

Synthesis of novel antibacterial and antifungal dithiocarbamate-containing piperazine derivatives via re-engineering multicomponent approach

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