Roberta J. Worthington Melander

Works (42)

Updated: August 2nd, 2023 21:15

2019 journal article

2-aminoimidazoles collapse mycobacterial proton motive force and block the electron transport chain

SCIENTIFIC REPORTS, 9.

By: A. Jeon *, D. Ackart*, W. Li *, M. Jackson *, R. Melander n, C. Melander n, R. Abramovitch *, A. Chicco *, R. Basaraba *, A. Obregon-Henao *

MeSH headings : Adenosine Triphosphate / metabolism; Antitubercular Agents / pharmacology; Biofilms / drug effects; Biofilms / growth & development; Electron Transport / drug effects; Humans; Imidazoles / pharmacology; Microbial Sensitivity Tests; Mycobacterium tuberculosis / drug effects; Mycobacterium tuberculosis / growth & development; Oxygen Consumption / drug effects; Proton-Motive Force / drug effects; Tuberculosis / drug therapy; Tuberculosis / microbiology
TL;DR: The mechanism of action of 2-AIs against M. tuberculosis is elucidates, providing a tool to better understand mycob bacterial bioenergetics and develop compounds with improved anti-mycobacterial activity. (via Semantic Scholar)
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Added: February 25, 2019

2019 journal article

Identification of Anti-Mycobacterial Biofilm Agents Based on the 2-Aminoimidazole Scaffold

CHEMMEDCHEM, 14(9), 927–937.

By: T. Nguyen  n, B. Minrovic*, R. Melander* & C. Melander*

author keywords: 2-aminoimidazoles; biofilms; mycobacteria; synergy; tuberculosis
MeSH headings : Animals; Antitubercular Agents / chemistry; Antitubercular Agents / pharmacology; Biofilms / drug effects; Imidazoles / chemistry; Male; Mice; Microsomes / drug effects; Microsomes / metabolism; Mycobacterium tuberculosis / drug effects
TL;DR: Using Mycobacterium smegmatis as a surrogate organism, the identification of two new 2‐aminoimidazole compounds are reported that inhibit and disperse mycobacterial biofilms, work synergistically with isoniazid and rifampicin to eradicate preformed M.’smegmatisBiofilms in vitro, are nontoxic toward Galleria mellonella, and exhibit stability in mouse plasma. (via Semantic Scholar)
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Added: July 1, 2019

2019 journal article

Small Molecule Potentiation of Gram-Positive Selective Antibiotics against Acinetobacter baumannii

ACS INFECTIOUS DISEASES, 5(7), 1223–1230.

By: S. Martin*, R. Melander*, C. Brackett n, A. Scott *, C. Chandler *, C. Nguyen  n, B. Minrovic*, S. Harrill n ...

author keywords: antibiotic adjuvant; antibiotic resistance; Acinetobacter baumannii; macrolide antibiotics; glycopeptide antibiotics; lipopolysaccharide
MeSH headings : Acinetobacter Infections / drug therapy; Acinetobacter baumannii / drug effects; Animals; Anti-Bacterial Agents / administration & dosage; Anti-Bacterial Agents / pharmacology; Bacterial Outer Membrane / drug effects; Disease Models, Animal; Drug Resistance, Multiple, Bacterial / drug effects; Drug Synergism; Glycopeptides / administration & dosage; Glycopeptides / pharmacology; Macrolides / administration & dosage; Macrolides / pharmacology; Microbial Sensitivity Tests; Moths; Small Molecule Libraries / administration & dosage; Small Molecule Libraries / pharmacology
TL;DR: Two adjuvant compounds are identified that dramatically enhance sensitivity of Acinetobacter baumannii to macrolide and glycopeptide antibiotics, with reductions in minimum inhibitory concentrations as high as 256-fold, and mode of action studies indicate that these adjuvants likely work by modulating lipopolysaccharide synthesis or assembly. (via Semantic Scholar)
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Added: August 5, 2019

2019 journal article

Using 2-aminobenzimidazole derivatives to inhibit Mycobacterium smegmatis biofilm formation

MEDCHEMCOMM, 10(3), 456–459.

By: T. Nguyen  n, M. Peszko  n, R. Melander* & C. Melander*

TL;DR: A series of 2-aminobenzimidazole (2-ABI) derivatives that potently inhibit biofilm formation by Mycobacterium smegmatis are reported on. (via Semantic Scholar)
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Added: April 22, 2019

2019 journal article

Using Small-Molecule Adjuvants to Repurpose Azithromycin for Use against Pseudomonas aeruginosa

ACS INFECTIOUS DISEASES, 5(1), 141–151.

By: V. Hubble*, B. Hubbard n, B. Minrovic*, R. Melander* & C. Melander*

author keywords: antibiotic resistance; antibiotic adjuvant; cystic fibrosis; Pseudomonas aeruginosa
MeSH headings : Adjuvants, Pharmaceutic / chemistry; Animals; Anti-Bacterial Agents / pharmacology; Azithromycin / pharmacology; Benzimidazoles / chemistry; Benzimidazoles / pharmacology; Cystic Fibrosis / drug therapy; Cystic Fibrosis / microbiology; Disease Models, Animal; Drug Repositioning; Larva / drug effects; Larva / microbiology; Microbial Sensitivity Tests; Moths / drug effects; Moths / microbiology; Pseudomonas aeruginosa / drug effects; Respiratory Tract Infections / drug therapy
TL;DR: A novel approach to combatting pseudomonal infections through the use of bis-2-aminoimidazole adjuvants that can potentiate the activity of a macrolide antibiotic commonly prescribed to CF patients as an anti-inflammatory agent is described. (via Semantic Scholar)
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Added: April 20, 2020

2018 review

Narrow-spectrum antibacterial agents

[Review of ]. MEDCHEMCOMM, 9(1), 12–21.

By: R. Melander n, D. Zurawski * & C. Melander n

TL;DR: The advantages and challenges of narrow-Spectrum antibacterial agents are outlined, the progress that has been made toward developing diagnostics to enable their use is discussed, and some of the narrow-spectrum antib bacterial agents currently being investigated against some ofThe most clinically important bacteria including Clostridium difficile, Mycobacterium tuberculosis and several ESKAPE pathogens are described. (via Semantic Scholar)
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Added: August 6, 2018

2018 journal article

Re-sensitizing Multidrug Resistant Bacteria to Antibiotics by Targeting Bacterial Response Regulators: Characterization and Comparison of Interactions between 2-Aminoimidazoles and the Response Regulators BfmR from Acinetobacter baumannii and QseB from Francisella spp.

FRONTIERS IN MOLECULAR BIOSCIENCES, 5.

By: M. Milton *, B. Minrovic n, D. Harris *, B. Kang*, D. Jung*, C. Lewis n, R. Thompson*, R. Melander n ...

author keywords: biofilms; antibiotic resistance; two-component systems; response regulators; Acinetobacter baumannii; Francisella
TL;DR: This work investigates the response regulator/2-AI interaction and looks at a wider library of 2-AI compounds, and establishes that Francisella tularensis/novicida, encoding for only three known response regulators, can be a model system to study the interaction between 2-AIs and response regulators. (via Semantic Scholar)
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Added: January 28, 2019

2017 journal article

2-aminoimidazoles potentiate beta-lactam antimicrobial activity against Mycobacterium tuberculosis by reducing beta-lactamase secretion and increasing cell envelope permeability

PLoS One, 12(7).

By: A. Jeon, A. Obregon-Henao, D. Ackart, B. Podell, J. Belardinelli, M. Jackson, T. Nguyen, M. Blackledge ...

Source: NC State University Libraries
Added: August 6, 2018

2017 journal article

Probing the Mechanism of LAL-32, a Gold Nanoparticle-Based Antibiotic Discovered through Small Molecule Variable Ligand Display

BIOCONJUGATE CHEMISTRY, 28(7), 1807–1810.

By: R. Byrne-Nash *, D. Lucero *, N. Osbaugh*, R. Melander n, C. Melander n & D. Feldheim*

MeSH headings : Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Cell Division / drug effects; Drug Discovery / methods; Drug Resistance, Bacterial; Escherichia coli / cytology; Escherichia coli / drug effects; Escherichia coli Proteins / antagonists & inhibitors; Gold; Ligands; Membrane Transport Proteins; Metal Nanoparticles / chemistry; Metal Nanoparticles / therapeutic use; Small Molecule Libraries
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Added: August 6, 2018

2017 journal article

Small molecule adjuvants that suppress both chromosomal and mcr-1 encoded colistin-resistance and amplify colistin efficacy in polymyxin-susceptible bacteria

BIOORGANIC & MEDICINAL CHEMISTRY, 25(20), 5749–5753.

By: W. Barker n, S. Martin n, C. Chandler *, T. Nguyen  n, T. Harris n, C. Goodell*, R. Melander n, Y. Doi *, R. Ernst *, C. Melander n

MeSH headings : Acinetobacter baumannii / drug effects; Adjuvants, Pharmaceutic / chemistry; Adjuvants, Pharmaceutic / pharmacology; Colistin / pharmacology; Drug Resistance, Bacterial / drug effects; Drug Resistance, Bacterial / genetics; Escherichia coli / drug effects; Escherichia coli Proteins / genetics; Escherichia coli Proteins / metabolism; Gram-Negative Bacteria / drug effects; Klebsiella pneumoniae / drug effects; Microbial Sensitivity Tests; Polymyxins / pharmacology; Small Molecule Libraries / chemistry; Small Molecule Libraries / pharmacology
TL;DR: This work reports successful reversion of mcr-1-driven colistin resistance in Acinetobacter baumannii, Klebsiella pneumoniae, and Escherichia coli with adjuvants reported as modulators of chromosomally-encoded colistIn resistance. (via Semantic Scholar)
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Added: August 6, 2018

2017 journal article

Structure of the Francisella response regulator QseB receiver domain, and characterization of QseB inhibition by antibiofilm 2-aminoimidazole-based compounds

MOLECULAR MICROBIOLOGY, 106(2), 223–235.

By: M. Milton *, C. Allen  n, E. Feldmann n, B. Bobay n, D. Jung*, M. Stephens n, R. Melander n, K. Theisen  n ...

MeSH headings : Anti-Bacterial Agents / pharmacology; Bacterial Proteins / chemistry; Bacterial Proteins / metabolism; Bacterial Proteins / ultrastructure; Biofilms / drug effects; Francisella tularensis / metabolism; Gene Expression Regulation, Bacterial / genetics; Imidazoles / metabolism; Imidazoles / pharmacology; Protein Binding; Virulence / drug effects; Virulence Factors / genetics; Virulence Factors / metabolism
TL;DR: It is shown that QseB interacts with 2‐aminoimidazole based compounds that impede its function, and this information will assist in tailoring compounds to act as adjuvants that will enhance the effect of antibiotics. (via Semantic Scholar)
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Added: August 6, 2018

2017 article

The Challenge of Overcoming Antibiotic Resistance: An Adjuvant Approach?

Melander, R. J., & Melander, C. (2017, August). ACS INFECTIOUS DISEASES, Vol. 3, pp. 559–563.

By: R. Melander n & C. Melander n

MeSH headings : Adjuvants, Pharmaceutic / pharmacology; Animals; Anti-Bacterial Agents / pharmacology; Drug Interactions; Drug Resistance, Bacterial / drug effects; Drug Resistance, Bacterial / physiology; Gram-Negative Bacteria / drug effects; Gram-Negative Bacteria / growth & development; Gram-Negative Bacteria / metabolism; Gram-Positive Bacteria / drug effects; Gram-Positive Bacteria / growth & development; Gram-Positive Bacteria / metabolism; Humans
TL;DR: Some of the advantages and disadvantages of the use of adjuvants, and various approaches to their identification are described, which have the potential to render an antibiotic against which bacteria have developed resistance once again effective. (via Semantic Scholar)
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Added: August 6, 2018

2017 journal article

The Discovery of 2-Aminobenzimidazoles That Sensitize Mycobacterium smegmatis and M. tuberculosis to beta-Lactam Antibiotics in a Pattern Distinct from beta-Lactamase Inhibitors

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 56(14), 3940–3944.

By: T. Nguyen  n, M. Blackledge *, E. Lindsey n, B. Minrovic n, D. Ackart*, A. Jeon *, A. Obregon-Henao *, R. Melander n, R. Basaraba *, C. Melander n

author keywords: aminobenzimidazoles; antibiotic resistance; medicinal chemistry; tuberculosis
MeSH headings : Anti-Bacterial Agents / chemical synthesis; Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Benzimidazoles / chemistry; Benzimidazoles / pharmacology; Drug Discovery; Lactams / chemical synthesis; Lactams / chemistry; Lactams / pharmacology; Molecular Structure; Mycobacterium smegmatis / drug effects; Mycobacterium smegmatis / enzymology; Mycobacterium tuberculosis / drug effects; Mycobacterium tuberculosis / enzymology; beta-Lactamase Inhibitors / chemical synthesis; beta-Lactamase Inhibitors / chemistry; beta-Lactamase Inhibitors / pharmacology; beta-Lactamases / metabolism
TL;DR: A library of 2-aminobenzimidazole derivatives was screened for the ability to suppress β-lactam resistance in Mycobacterium smegmatis and preliminary mechanistic studies revealed that the lead compounds act through a mechanism distinct from that of traditional β- lactamase inhibitors. (via Semantic Scholar)
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Added: August 6, 2018

2016 journal article

Marine sponge alkaloids as a source of anti-bacterial adjuvants

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 26(24), 5863–5866.

By: R. Melander n, H. Liu *, M. Stephens n, C. Bewley * & C. Melander n

author keywords: Marine sponge; Pyrrole-imidazole alkaloid; Biofilm; Antibiotic; Adjuvant
MeSH headings : Acinetobacter baumannii / drug effects; Alkaloids / chemistry; Alkaloids / metabolism; Alkaloids / pharmacology; Animals; Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / metabolism; Anti-Bacterial Agents / pharmacology; Dose-Response Relationship, Drug; Imidazoles / chemistry; Imidazoles / pharmacology; Methicillin-Resistant Staphylococcus aureus / drug effects; Microbial Sensitivity Tests; Molecular Structure; Porifera; Pyrroles / chemistry; Pyrroles / pharmacology; Structure-Activity Relationship
TL;DR: The potential of marine secondary metabolites to serve as a source of non-traditional anti-bacterial agents is demonstrated by showing that pyrrole-imidazole alkaloids inhibit biofilm formation and suppress antibiotic resistance. (via Semantic Scholar)
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Added: August 6, 2018

2016 journal article

Potentiation of Francisella resistance to conventional antibiotics through small molecule adjuvants

MEDCHEMCOMM, 7(1), 128–131.

By: M. Stephens n, V. Hubble n, R. Ernst *, M. Hoek *, R. Melander n, J. Cavanagh n, C. Melander n

TL;DR: A screen of 20 compounds identified small molecule adjuvants capable of potentiating anitbiotic activty against Francisella philomiragia and led to the discovery of a potentially new class of small molecule aduvants containg an indole core. (via Semantic Scholar)
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Added: August 6, 2018

2016 journal article

Second generation modifiers of colistin resistance show enhanced activity and lower inherent toxicity

TETRAHEDRON, 72(25), 3549–3553.

By: C. Brackett n, R. Furlani n, R. Anderson  n, A. Krishnamurthy n, R. Melander n, S. Moskowitz *, R. Ernst *, C. Melander n

author keywords: Antibiotic adjuvant; 2-Aminoimidazole; Colistin; ESKAPE pathogens; Acinetobacter baumannii; Pseudomonas aeruginosa
TL;DR: From these libraries, a new small molecule was identified that lowers the minimum inhibitory concentration of colistin by up to 32-fold greater than the parent compound while also displaying less inherent bacterial effect, thereby minimizing the likelihood of resistance evolution. (via Semantic Scholar)
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Added: August 6, 2018

2015 article

From Worms to Targeting Virulence Factors

Melander, R. J., & Melander, C. (2015, April 23). CHEMISTRY & BIOLOGY, Vol. 22, pp. 436–437.

By: R. Melander n & C. Melander n

MeSH headings : Animals; Bacterial Proteins / metabolism; Caenorhabditis elegans / microbiology; Metalloendopeptidases / metabolism; Pseudomonas aeruginosa / physiology; Virulence Factors / metabolism
TL;DR: A Caenorhabditis elegans model is used to validate the Pseudomonas aeruginosa virulence factor LasB as a potential therapeutic target and to identify a LasB inhibitor with in-vivo efficacy. (via Semantic Scholar)
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Added: August 6, 2018

2015 journal article

Inhibition and breaking of advanced glycation end-products (AGEs) with bis-2-aminoimidazole derivatives

TETRAHEDRON LETTERS, 56(23), 3406–3409.

By: M. Richardson*, R. Furlani n, B. Podell *, D. Ackart*, J. Haugen*, R. Melander n, C. Melander n, R. Basaraba *

author keywords: Advanced glycation end-products (AGES); Bis-2-aminoimidazole; Aminoguanidine; Diabetes
TL;DR: The screening of a series of 2-aminoimidazloles for anti-AGE activity is reported, and the identification of a bis-2-aminosidazole lead compound that possesses superior AGE inhibition and breaking activity compared to the known AGE inhibitor aminoguanidine is identified. (via Semantic Scholar)
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Added: August 6, 2018

2015 journal article

Innovative strategies for combating biofilm-based infections

Biofilm-Based Healthcare-Associated Infections, Vol Ii, 831, 69–91.

By: R. Melander & C. Melander

Source: NC State University Libraries
Added: August 6, 2018

2015 journal article

Second generation 2-aminoimidazole based advanced glycation end product inhibitors and breakers

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 25(21), 4820–4823.

By: R. Furlani n, M. Richardson*, B. Podell *, D. Ackart*, J. Haugen*, R. Melander n, R. Basaraba *, C. Melander n

author keywords: Advanced glycation end-product (AGE); 2-Aminoimidazole; Akabori; Diabetes
MeSH headings : Glycation End Products, Advanced / antagonists & inhibitors; Glycation End Products, Advanced / metabolism; Imidazoles / chemical synthesis; Imidazoles / chemistry; Imidazoles / pharmacology; Molecular Structure; Structure-Activity Relationship
TL;DR: The use of a rapid, scalable, two-step procedure is reported to access a second generation of 2-AI based anti-AGE compounds from commercially available amino acids that exhibit increased AGE inhibition and breaking activty compared to the first generation compounds. (via Semantic Scholar)
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Added: August 6, 2018

2015 article

Small Steps to New Drugs for Bugs

Melander, R. J., & Selwood, D. L. (2015, January). CHEMICAL BIOLOGY & DRUG DESIGN, Vol. 85, pp. 1–3.

By: R. Melander n & D. Selwood

author keywords: antibacterial drug discovery; antibiotic resistance; novel antibacterial strategies
MeSH headings : Anti-Bacterial Agents; Drug Design; Drug Discovery / trends; Drug Resistance, Bacterial; Humans
TL;DR: Diverse review articles on topics from economics and pricing to new discovery methods are brought together in this special issue of The Lancet Infectious Diseases. (via Semantic Scholar)
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Added: August 6, 2018

2014 journal article

Controlling bacterial behavior with indole-containing natural products and derivatives

TETRAHEDRON, 70(37), 6363–6372.

By: R. Melander n, M. Minvielle n & C. Melander n

author keywords: Indole; Bacterial communication; Anti-virulence; Biofilm; Antibiotic resistance
TL;DR: An overview of the process controlled by indole signaling is given, current efforts to design indole-containing small molecules to intercept these pathways are summarized, and the synthetic efforts towards accessing indole derived bioactive small molecules are detailed. (via Semantic Scholar)
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Added: August 6, 2018

2014 journal article

Disruption of heterotypic community development by Porphyromonas gingivalis with small molecule inhibitors

MOLECULAR ORAL MICROBIOLOGY, 29(5), 185–193.

By: C. Wright*, H. Wu, R. Melander n, C. Melander  n & J. Lamont *

author keywords: biofilms; periodontal disease; porphyromonas; streptococcus; fimbriae
MeSH headings : Bacterial Adhesion / drug effects; Bacterial Proteins / antagonists & inhibitors; Bacterial Proteins / drug effects; Benzimidazoles / pharmacology; Biofilms / drug effects; Carbon-Sulfur Lyases / drug effects; Fimbriae Proteins / antagonists & inhibitors; Humans; Image Processing, Computer-Assisted / methods; Imaging, Three-Dimensional / methods; Imidazoles / pharmacology; Microbial Interactions; Microscopy, Confocal / methods; Pili, Sex / drug effects; Porphyromonas gingivalis / drug effects; Porphyromonas gingivalis / physiology; Pyrroles / pharmacology; Small Molecule Libraries; Streptococcus gordonii / physiology
TL;DR: The potential for a small molecular inhibitor-based approach to the prevention of diseases associated with Porphyromonas gingivalis is demonstrated. (via Semantic Scholar)
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Added: August 6, 2018

2014 journal article

Reversal of Mycobacterium tuberculosis phenotypic drug resistance by 2-aminoimidazole- based small molecules

PATHOGENS AND DISEASE, 70(3), 370–378.

By: D. Ackart*, E. Lindsey n, B. Podell *, R. Melander n, R. Basaraba * & C. Melander n

author keywords: tuberculosis; drug tolerant; biofilm; 2-aminoimidazole; drug resistant; isoniazid
MeSH headings : Antitubercular Agents / chemistry; Antitubercular Agents / pharmacology; Biofilms / drug effects; Biofilms / growth & development; Drug Resistance, Bacterial; Humans; Imidazoles / chemistry; Imidazoles / pharmacology; Microbial Sensitivity Tests; Mycobacterium smegmatis / drug effects; Mycobacterium smegmatis / physiology; Mycobacterium tuberculosis / drug effects; Mycobacterium tuberculosis / physiology; Phenotype
TL;DR: 2-aminoimidazole-based small molecules as an adjunct to antimicrobial treatment has the potential to be an effective antituberculosis treatment strategy designed specifically to eradicate drug-tolerant M. tuberculosis. (via Semantic Scholar)
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Added: August 6, 2018

2014 journal article

Small Molecule Downregulation of PmrAB Reverses Lipid A Modification and Breaks Colistin Resistance

ACS CHEMICAL BIOLOGY, 9(1), 122–127.

By: T. Harris n, R. Worthington n, L. Hittle*, D. Zurawski *, R. Ernst * & C. Melander n

MeSH headings : Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Bacterial Proteins / genetics; Colistin / chemistry; Colistin / pharmacology; Down-Regulation / drug effects; Drug Resistance, Multiple, Bacterial / drug effects; Gram-Negative Bacteria / drug effects; Gram-Negative Bacteria / genetics; Gram-Negative Bacteria / metabolism; Gram-Negative Bacterial Infections / drug therapy; Humans; Lipid A / metabolism; Small Molecule Libraries / chemistry; Small Molecule Libraries / pharmacology; Transcription Factors / genetics
TL;DR: This report reports a small molecule adjuvant that suppresses colistin resistance in multidrug resistant Acinetobacter baumannii and Klebsiella pneumoniae by interfering with the expression of a two-component system. (via Semantic Scholar)
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Added: August 6, 2018

2014 journal article

Small-Molecule Suppression of beta-Lactam Resistance in Multidrug-Resistant Gram-Negative Pathogens

JOURNAL OF MEDICINAL CHEMISTRY, 57(17), 7450–7458.

By: C. Brackett n, R. Melander n, I. An n, A. Krishnamurthy n, R. Thompson n, J. Cavanagh n, C. Melander n

MeSH headings : Animals; Cell Line; Cell Survival / drug effects; Drug Resistance, Multiple, Bacterial / drug effects; Gram-Negative Bacteria / classification; Gram-Negative Bacteria / drug effects; Hemolysis / drug effects; Humans; Keratinocytes / cytology; Keratinocytes / drug effects; Microbial Sensitivity Tests; Sheep; Small Molecule Libraries / chemistry; Small Molecule Libraries / pharmacology; beta-Lactam Resistance / drug effects
TL;DR: A small molecule was identified from this library of aryl amide 2-aminoimidazoles that is capable of lowering the minimum inhibitory concentration of β-lactam antibiotics by up to 64-fold. (via Semantic Scholar)
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Added: August 6, 2018

2014 journal article

Thiol-modified gold nanoparticles for the inhibition of Mycobacterium smegmatis

CHEMICAL COMMUNICATIONS, 50(100), 15860–15863.

By: J. Gifford *, J. Bresee*, C. Carter*, G. Wang *, R. Melander n, C. Melander n, D. Feldheim*

MeSH headings : Cell Line; Cell Survival / drug effects; Erythrocytes / cytology; Erythrocytes / drug effects; Gold / chemistry; Hemolysis / drug effects; Humans; Metal Nanoparticles / chemistry; Metal Nanoparticles / toxicity; Microbial Sensitivity Tests; Mycobacterium smegmatis / drug effects; Sulfhydryl Compounds / chemistry
TL;DR: It is demonstrated that the Small Molecule Variable Ligand Display (SMLVD) method for nanoparticle antibiotic discovery can be expanded around a ligand feed ratio parameter space to identify gold nanoparticle conjugates that are potent inhibitors of mycobacteria growth. (via Semantic Scholar)
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Added: August 6, 2018

2013 journal article

Biologically inspired strategies for combating bacterial biofilms

CURRENT OPINION IN PHARMACOLOGY, 13(5), 699–706.

By: M. Blackledge n, R. Worthington n & C. Melander n

MeSH headings : Animals; Anti-Bacterial Agents / pharmacology; Anti-Bacterial Agents / therapeutic use; Bacterial Infections / drug therapy; Bacterial Infections / metabolism; Bacterial Physiological Phenomena / drug effects; Biofilms / drug effects; Humans; Quorum Sensing / drug effects; Signal Transduction / drug effects
TL;DR: Small molecule interference with bacterial communication and signaling pathways, including quorum sensing and two-component signal transduction systems are focused on, focusing firstly on enzymatic approaches to the degradation of extracellular matrix components to effect biofilm dispersal. (via Semantic Scholar)
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Added: August 6, 2018

2013 review

Combination approaches to combat multidrug-resistant bacteria

[Review of ]. TRENDS IN BIOTECHNOLOGY, 31(3), 177–184.

By: R. Worthington n & C. Melander n

author keywords: antibiotic resistance; antibiotic adjuvant
MeSH headings : Adjuvants, Pharmaceutic / therapeutic use; Anti-Bacterial Agents / therapeutic use; Bacterial Infections / drug therapy; Bacterial Infections / microbiology; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination / methods; Humans
TL;DR: Recent developments toward combination therapies for the treatment of multidrug-resistant bacterial infections are described, and the development of adjuvants that either directly target resistance mechanisms such as the inhibition of β-lactamase enzymes, or indirectly target resistance by interfering with bacterial signaling pathways such as two-component systems (TCSs). (via Semantic Scholar)
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Added: August 6, 2018

2013 journal article

N-Substituted 2-aminoimidazole inhibitors of MRSA biofilm formation accessed through direct 1,3-bis(tert-butoxycarbonyl)guanidine cyclization

ORGANIC & BIOMOLECULAR CHEMISTRY, 11(1), 130–137.

By: A. Yeagley  n, Z. Su n, K. McCullough n, R. Worthington n & C. Melander n

MeSH headings : Anti-Bacterial Agents / chemical synthesis; Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Biofilms / drug effects; Biofilms / growth & development; Cyclization; Guanidines / chemistry; Imidazoles / chemical synthesis; Imidazoles / chemistry; Imidazoles / pharmacology; Methicillin-Resistant Staphylococcus aureus / drug effects; Molecular Structure; Structure-Activity Relationship; Triazoles / chemical synthesis; Triazoles / chemistry; Triazoles / pharmacology
TL;DR: A library of N-substituted derivatives of a previously reported 2-aminoimidazole/triazole (2-AIT) biofilm modulator exhibited synergistic activity with oxacillin against planktonic MRSA and has the potential to be used as adjuvants with conventional antibiotics. (via Semantic Scholar)
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2013 journal article

Overcoming Resistance to beta-Lactam Antibiotics

JOURNAL OF ORGANIC CHEMISTRY, 78(9), 4207–4213.

By: R. Worthington n & C. Melander n

MeSH headings : Anti-Bacterial Agents / chemical synthesis; Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Drug Discovery; Molecular Structure; Small Molecule Libraries / chemical synthesis; Small Molecule Libraries / chemistry; Small Molecule Libraries / pharmacology; beta-Lactam Resistance / drug effects; beta-Lactamase Inhibitors; beta-Lactams / chemical synthesis; beta-Lactams / chemistry; beta-Lactams / pharmacology
TL;DR: Small molecule strategies to overcome resistance to β-lactam antibiotics include the development of β- lactamase inhibitors and compounds that interfere with the ability of the bacteria to sense an antibiotic threat and activate their resistance mechanisms. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2013 review

Small-molecule inhibition of bacterial two-component systems to combat antibiotic resistance and virulence

[Review of ]. FUTURE MEDICINAL CHEMISTRY, 5(11), 1265–1284.

By: R. Worthington n, M. Blackledge n & C. Melander n

MeSH headings : Bacteria / metabolism; Bacteria / pathogenicity; Bacterial Infections / drug therapy; Bacterial Proteins / antagonists & inhibitors; Bacterial Proteins / metabolism; Biofilms / drug effects; Drug Resistance, Multiple, Bacterial / drug effects; Histidine Kinase; Humans; Protein Kinases / chemistry; Protein Kinases / metabolism; Signal Transduction / drug effects; Small Molecule Libraries / chemistry; Small Molecule Libraries / pharmacology; Small Molecule Libraries / therapeutic use; Virulence / drug effects
TL;DR: An overview of TCS that are potential targets for such a strategy, small-molecules inhibitors of T CS identified to date are described, and assays for the identification of novel inhibitors are discussed. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2012 journal article

2-Aminopyrimidine as a novel scaffold for biofilm modulation

Organic & Biomolecular Chemistry, 10(13), 2552–2561.

By: E. Lindsey, R. Worthington, C. Alcaraz & C. Melander

Source: NC State University Libraries
Added: August 6, 2018

2012 journal article

Deconvoluting Interspecies Bacterial Communication

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 51(26), 6314–6315.

By: R. Worthington n & C. Melander n

author keywords: autoinducer-2; bacterial communication; 4; 5-dihydroxy-2; 3-pentanedione; NMR spectroscopy; quorum sensing
MeSH headings : Bacteria / chemistry; Pentanes / analysis; Quorum Sensing; Signal Transduction
TL;DR: NMR spectroscopy has now been used to establish that the extent of the structural diversity displayed by DPD over a broad pH range is even greater than previously posited. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
15. Life on Land (OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2012 journal article

Exploring the Interaction Between siRNA and the SMoC Biomolecule Transporters: Implications for Small Molecule-Mediated Delivery of siRNA

CHEMICAL BIOLOGY & DRUG DESIGN, 79(1), 9–21.

By: M. Gooding *, S. Tudzarova *, R. Worthington n, S. Kingsbury *, A. Rebstock*, H. Dube *, M. Simone *, C. Visintin* ...

author keywords: calorimetric techniques; chemical biology; molecular modeling; nanotechnology (drug discovery); RNAi and antisense techniques
MeSH headings : Cell Cycle Proteins / antagonists & inhibitors; Cell Cycle Proteins / genetics; Cell Cycle Proteins / metabolism; Cell Line; Guanidine / chemistry; Humans; Kinetics; Microscopy, Confocal; Molecular Dynamics Simulation; Protein Serine-Threonine Kinases / antagonists & inhibitors; Protein Serine-Threonine Kinases / genetics; Protein Serine-Threonine Kinases / metabolism; RNA Interference; RNA, Small Interfering / chemistry; RNA, Small Interfering / metabolism; Small Molecule Libraries / chemical synthesis; Small Molecule Libraries / chemistry
TL;DR: Improved synthetic route to small molecule carriers is shown, including Molander chemistry using trifluoroborate salts to improve the yield of the Suzuki–Miyaura coupling step for the formation of the biphenyl backbone, and Knockdown of Cdc7 kinase, a target for cancer, is achieved. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2012 journal article

Foliar-Applied Small Molecule that Suppresses Biofilm Formation and Enhances Control of Copper-Resistant Xanthomonas euvesicatoria on Pepper

PLANT DISEASE, 96(11), 1638–1644.

By: R. Worthington, S. Rogers*, R. Huigens*, C. Melander* & D. Ritchie n

TL;DR: A small molecule additive, a member of the 2-aminoimidazole (2AI) group that is an analogue of the marine sponge natural product oroidin that suppresses resistance of Xanthomonas euvesicatoria to copper and decreases biofilm formation in an in vitro system is reported. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
14. Life Below Water (OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2012 journal article

Potent Small-Molecule Suppression of Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 51(45), 11254–11257.

By: T. Harris n, R. Worthington n & C. Melander n

author keywords: 2-aminoimidazoles; adjuvants; antibiotics; antibiotic resistance; MRSA
MeSH headings : Anti-Bacterial Agents / pharmacology; Drug Resistance; Methicillin-Resistant Staphylococcus aureus / drug effects; Microbial Sensitivity Tests; Oxacillin / pharmacology
TL;DR: A potent small molecule is pictured that, at sub-minimum inhibitory concentration levels, lowers the MIC of oxacillin against a number of MRSA strains by up to 512-fold. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2012 journal article

Small Molecule Suppression of Carbapenem Resistance in NDM-1 Producing Klebsiella pneumoniae

ACS MEDICINAL CHEMISTRY LETTERS, 3(5), 357–361.

By: R. Worthington n, C. Bunders n, C. Reed n & C. Melander n

author keywords: NDM-1; Klebsiella pneumoniae; antibiotic adjuvant; resistance suppression; 2-aminoimidazole
TL;DR: A 2-aminoimidazole derived small molecule is identified that acts as an antibiotic adjuvant and is able to suppress resistance of a NDM-1 producing strain of K. pneumoniae, able to lower carbapenem minimum inhibitory concentrations by up to 16-fold while exhibiting little bactericidal activity itself. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
3. Good Health and Well-being (Web of Science; OpenAlex)
Source: Web Of Science
Added: August 6, 2018

2012 journal article

Small molecule control of bacterial biofilms

Organic & Biomolecular Chemistry, 10(37), 7457–7474.

By: R. Worthington, J. Richards & C. Melander

Source: NC State University Libraries
Added: August 6, 2018

2011 journal article

A facile synthesis of 1,5-disubstituted-2-aminoimidazoles: Antibiotic activity of a first generation library

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 21(15), 4516–4519.

By: T. Harris n, R. Worthington n & C. Melander n

author keywords: 2-Aminoimidazole; Amino aldehyde; Biofilm; Antibiotic
MeSH headings : Anti-Bacterial Agents / chemical synthesis; Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Drug Resistance, Multiple, Bacterial / drug effects; Imidazoles / chemical synthesis; Imidazoles / chemistry; Imidazoles / pharmacology; Microbial Sensitivity Tests; Structure-Activity Relationship
TL;DR: An efficient synthetic route to 1,5-disubstituted 2-aminoimidazoles from readily available amino acids and aldehydes has been developed and several compounds were shown to exhibit notable antibiotic activity against a variety of bacterial strains including multi-drug resistant isolates. (via Semantic Scholar)
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Source: Web Of Science
Added: August 6, 2018

2011 journal article

Evaluation of 4,5-Disubstituted-2-Aminoimidazole-Triazole Conjugates for Antibiofilm/Antibiotic Resensitization Activity Against MRSA and Acinetobacter baumannii

CHEMMEDCHEM, 6(12), 2243–2251.

By: Z. Su n, L. Peng n, R. Worthington n & C. Melander n

author keywords: aminoimidazoles; antibiotic resensitization; biofilms; MRSA; synergism
MeSH headings : Acinetobacter baumannii / drug effects; Acinetobacter baumannii / physiology; Anti-Bacterial Agents / chemical synthesis; Anti-Bacterial Agents / chemistry; Anti-Bacterial Agents / pharmacology; Biofilms / drug effects; Imidazoles / chemistry; Methicillin-Resistant Staphylococcus aureus / drug effects; Methicillin-Resistant Staphylococcus aureus / physiology; Oxacillin / chemistry; Oxacillin / pharmacology; Structure-Activity Relationship; Triazoles / chemistry
TL;DR: This class of small molecules was found to inhibit biofilm formation by methicillin‐resistant Staphylococcus aureus (MRSA) at low‐micromolar concentrations and the ability of selected compounds to resensitize MRSA to traditional antibiotics (resensitization activity) was determined. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
Source: Web Of Science
Added: August 6, 2018

2011 journal article

Intercepting Bacterial Indole Signaling with Flustramine Derivatives

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 133(50), 20160–20163.

By: C. Bunders n, M. Minvielle n, R. Worthington n, M. Ortiz n, J. Cavanagh n & C. Melander n

MeSH headings : Escherichia coli / metabolism; Hydrocarbons, Brominated / metabolism; Indole Alkaloids / metabolism; Indoles / metabolism; Signal Transduction; Staphylococcus aureus / metabolism
TL;DR: DFBr derivatives are found that are 10-1000 times more active than indole itself, demonstrating that the flustramine family of indolic natural products represent a privileged scaffold for the design of molecules to control pathogenic bacterial behavior. (via Semantic Scholar)
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UN Sustainable Development Goal Categories
Source: Web Of Science
Added: August 6, 2018

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