Rapid kill assessment of an<i>N</i>-arylated NH125 analogue against drug-resistant microorganisms

Abouelhassan, Yasmeen; Zhang, Peilan; Ding, Yousong; Huigens, Robert W.

doi:10.1039/c8md00613j

Cited by 4 publications

(5 citation statements)

References 29 publications

(34 reference statements)

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“…In addition, the lengths of seedlings that were treated with CS-g-poly (MA-co-AN) HA at concentrations of 500 µg were significantly shorter than those of the non-treated controls ( Figure 3 D). CS-g-poly (MA-co-AN) HA showed similar safety profile as reported for CS-based nanocarriers and halogenated molecules in previous reports [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Thus, based on these comparative observations, it can be suggested that the prepared complex is safe for further application in drug delivery as well as environmental applications.…”

Section: Resultssupporting

confidence: 83%

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Grafted Chitosan-Hyaluronic Acid (CS-g-poly (MA-co-AN) HA) Complex Inhibits Fluconazole-Resistant Candida albicans Biofilm Formation

et al. 2022

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Fungal resistance that leads to the failure of drug therapy due to biofilm development is a major clinical challenge. Various polysaccharides have been used to control biofilm formation by drug-resistant fungi, and this study was undertaken to develop chitosan (CS)-modified materials and evaluate their abilities to inhibit Candida biofilm growth. CS was grafted with methacrylamide (MA) and acrylonitrile (AN) and, to improve its application characteristics further, was grafted with hyaluronic acid to produce CS-g-poly (MA-co-AN) HA complex. Grafting and complex formation were confirmed using spectroscopic techniques. CS-g-poly (MA-co-AN) HA was tested to investigate its ability to inhibit Candida albicans biofilm formation and showed significant antibiofilm activity at 200 µg/mL. Additionally, CS-g-poly (MA-co-AN) HA did not have any toxic effect on Caenorhabditis elegans. Thus, this study provides an innovative means of preventing microorganism-associated biofilm formation.

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Section: Resultssupporting

confidence: 83%

“…To determine the killing efficacy of CS-g-poly (MA-co-AN) HA, a time-kill kinetic assay was used, as previously described [ 23 , 24 ]. Briefly, overnight cultures of C. albicans DAY 185 at a dilution of 1:50 inoculated in PDB were used for assays.…”

Section: Methodsmentioning

confidence: 99%

Grafted Chitosan-Hyaluronic Acid (CS-g-poly (MA-co-AN) HA) Complex Inhibits Fluconazole-Resistant Candida albicans Biofilm Formation

et al. 2022

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“…Cytotoxicity Assay against HEK-293 Cells. 48 The viability of HEK-293 cells was assessed by the MTT assay. The cells were cultured in DMEM medium containing 10% fetal bovine serum and 100 U/mL penicillin and streptomycin.…”

Section: -(Ethylthiomentioning

confidence: 99%

“…From this series, 12 new HPs and parent HP 3 were evaluated against mammalian cell lines, including (1) three nonbrominated 3-chloro HPs (subseries A; 21 , 24 , and 27 ), (2) eight 2,4-dibromo-3-chloro HPs (subseries B; 28–35 ), and (3) one 2,4-dibromo-3-thiol HP (subseries C; 45 ). The cell lines used to determine cytotoxicity of HPs included HeLa (cervical cancer cell line; 24 h LDH release assay, HPs were evaluated at 25, 50, and 100 μM), J774 MΦ (macrophages; 24 h Alamar Blue assay, HPs tested in twofold dilutions up to 200 μM), HepG2 (hepatocellular carcinoma; 24 h Alamar Blue assay, HPs tested in twofold dilutions up to 200 μM), and HEK-293 (human embryonic kidney cells; 72 h MTT assay only HP 29 was evaluated in twofold dilutions up to 200 μM).…”

Section: Introductionmentioning

confidence: 99%

A Modular Synthetic Route Involving N-Aryl-2-nitrosoaniline Intermediates Leads to a New Series of 3-Substituted Halogenated Phenazine Antibacterial Agents

et al. 2021

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Pathogenic bacteria demonstrate incredible abilities to evade conventional antibiotics through the development of resistance and formation of dormant, surface-attached biofilms. Therefore, agents that target and eradicate planktonic and biofilm bacteria are of significant interest. We explored a new series of halogenated phenazines (HP) through the use of N-aryl-2nitrosoaniline synthetic intermediates that enabled functionalization of the 3-position of this scaffold. Several HPs demonstrated potent antibacterial and biofilm-killing activities (e.g., HP 29, against methicillin-resistant Staphylococcus aureus: MIC = 0.075 μM; MBEC = 2.35 μM), and transcriptional analysis revealed that HPs 3, 28, and 29 induce rapid iron starvation in MRSA biofilms. Several HPs demonstrated excellent activities against Mycobacterium tuberculosis (HP 34, MIC = 0.80 μM against CDC1551). This work established new SAR insights, and HP 29 demonstrated efficacy in dorsal wound infection models in mice. Encouraged by these findings, we believe that HPs could lead to significant advances in the treatment of challenging infections.

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“…Eprosartan mesylate is an angiotensin II receptor antagonist used to treat high blood pressure [ 12 ]. NH125 is a selective inhibitor of eukaryotic elongation factor 2 kinase with anti-bacterial properties [ 13 ]. Drofenine hydrochloride is a competitive inhibitor of butyrylcholinesterase [ 14 ].…”

Section: Resultsmentioning

confidence: 99%

YM155 Inhibits NleB and SseK Arginine Glycosyltransferase Activity

et al. 2021

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The type III secretion system effector proteins NleB and SseK are glycosyltransferases that glycosylate protein substrates on arginine residues. We conducted high-throughput screening assays on 42,498 compounds to identify NleB/SseK inhibitors. Such small molecules may be useful as mechanistic probes and may have utility in the eventual development of anti-virulence therapies against enteric bacterial pathogens. We observed that YM155 (sepantronium bromide) inhibits the activity of Escherichia coli NleB1, Citrobacter rodentium NleB, and both Salmonella enterica SseK1 and SseK2. YM155 was not toxic to mammalian cells, nor did it show cross-reactivity with the mammalian O-linked N-acetylglucosaminyltransferase (OGT). YM155 reduced Salmonella survival in mouse macrophage-like cells but had no direct impact on bacterial growth rates, suggesting YM155 may have utility as a potential anti-virulence inhibitor.

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Rapid kill assessment of anN-arylated NH125 analogue against drug-resistant microorganisms

Abstract: N-Arylated NH125 analogue 1 rapidly eradicates a diverse panel of drug-resistant bacteria and fungi (≥99.9% kill in 1 to 10 minutes).

Cited by 4 publications

References 29 publications

Grafted Chitosan-Hyaluronic Acid (CS-g-poly (MA-co-AN) HA) Complex Inhibits Fluconazole-Resistant Candida albicans Biofilm Formation

Grafted Chitosan-Hyaluronic Acid (CS-g-poly (MA-co-AN) HA) Complex Inhibits Fluconazole-Resistant Candida albicans Biofilm Formation

A Modular Synthetic Route Involving N-Aryl-2-nitrosoaniline Intermediates Leads to a New Series of 3-Substituted Halogenated Phenazine Antibacterial Agents

YM155 Inhibits NleB and SseK Arginine Glycosyltransferase Activity

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