Discovery and Characterization of Potent Thiazoles versus Methicillin- and Vancomycin-Resistant <i>Staphylococcus aureus</i>

Mohammad, Haroon; Mayhoub, Abdelrahman S.; Ghafoor, A.; Soofi, Muhammad A.; Alajlouni, Ruba A.; Cushman, Mark; Seleem, Mohamed N.

doi:10.1021/jm401905m

Cited by 96 publications

(123 citation statements)

References 19 publications

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“…The detailed synthetic protocols and spectral data of final products 1 and 2 as well as all intermediates have been previously reported 16,17 .…”

Section: Methodsmentioning

confidence: 99%

“…To assess the ability of compound 2 to passively permeate through epithelial tissue, a Caco-2 permeability assay was performed as described previously 16 . Caco-2 cells grown in tissue culture flasks were trypsinized, suspended in medium, and the suspensions were applied to wells of a Millipore 96 well Caco-2 plate.…”

Section: Methodsmentioning

confidence: 99%

“…We recently discovered a novel lead thiazole compound 1 which exhibited potent antimicrobial activity against MRSA (Figure 1) 16 . The lead compound is composed of a thiazole nucleus connected to a cationic amino head at the C5-position and a lipophilic phenylalkyl tail at the C2-position.…”

Section: Introductionmentioning

confidence: 99%

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Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci

et al. 2014

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Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates. Additionally, the anti-biofilm activity of the novel thiazoles was investigated against Staphylococcus epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to re-sensitize VRSA to vancomycin, reducing its minimum inhibitory concentration (MIC) by 512-fold in two strains. Additionally, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively the results obtained demonstrate compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm.

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“…The detailed synthetic protocols and spectral data of final products 1 and 2 as well as all intermediates have been previously reported 16,17 .…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci

et al. 2014

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“…There is a huge global concern about the increased drug resistance S. aureus and development of multiple resistance in several drugs such as penicillins, tetracyclines, macrolides and aminoglycosides [5], [6].…”

Section: Introductionmentioning

confidence: 99%

Identification of tigecycline- and vancomycin-resistant Staphylococcus aureus strains among patients with urinary tract infection in Iran

Yousefi

Fallah

Arshadi

et al. 2017

New Microbes and New Infections

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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital- and community-acquired infections worldwide. Although S. aureus rarely accounts for urinary tract infections (UTI), untreated UTI can lead to several complications. For decades vancomycin has been used for the treatment of MRSA infections. This study was performed to assess the in vitro activity of vancomycin, tigecycline, linezolid and quinupristin/dalfopristin against MRSA isolates from UTI patients. Thirty MRSA strains from 54 S. aureus isolates were isolated from patients with UTI. The antimicrobial susceptibility patterns of the strains were determined by the Kirby-Bauer disk diffusion and broth microdilution methods. PCR assays were used to detect the vanA gene. The MRSA isolates resistant to vancomycin were confirmed using the broth microdilution method. The results revealed that the MRSA isolates were 100% susceptible to linezolid and quinupristin/dalfopristin but 93.3% susceptible to vancomycin and tigecycline respectively. The broth microdilution method confirmed two MRSA strains (6.6%) to be resistant to vancomycin and tigecycline. The study identified vancomycin resistance among the MRSA isolates from UTI patients. This vancomycin resistance in MRSA isolates poses a challenge in managing S. aureus infections. Our study's results highlight the need to correctly identify patients in whom last-resort therapy such as linezolid and quinupristin/dalfopristin should be administered.

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“…The aqueous solubility of 4b was evaluated using a standard turbidometric solubility assay in phosphate-buffered saline (PBS), using a previously described method 41 . Briefly, serial dilutions of 4b and control drugs (tamoxifen and verapamil) were prepared in dimethyl sulfoxide.…”

Section: Methodsmentioning

confidence: 99%

Discovery of a Novel Dibromoquinoline Compound Exhibiting Potent Antifungal and Antivirulence Activity That Targets Metal Ion Homeostasis

et al. 2018

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Globally, invasive fungal infections pose a significant challenge to modern human medicine due to the limited number of antifungal drugs and the rise in resistance to current antifungal agents. The vast majority of invasive fungal infections are caused by species of Candida, Cryptococcus, and Aspergillus. Novel antifungal molecules consisting of unexploited chemical scaffolds with a unique mechanism are a pressing need. The present study identifies a dibromoquinoline compound (4b) with broad-spectrum antifungal activity that inhibits growth of pertinent species of Candida (chiefly C. albicans), Cryptococcus, and Aspergillus at a concentration as low as 0.5 μg/mL. Furthermore, 4b, at a subinhibitory concentration, interfered with expression of two key virulence factors (hyphae and biofilm formation) involved in C. albicans pathogenesis. Three yeast deletion strains (cox17Δ, ssa1Δ, aft2Δ) related to metal ion homeostasis were found to be highly-sensitive to 4b in growth assays indicating the compound exerts its antifungal effect through a unique, previously unexploited mechanism. Supplementing the media with either copper or iron ions reversed the strain sensitivity to 4b further corroborating that the compound targets metal ion homeostasis. 4b’s potent antifungal activity was validated in vivo, as the compound enhanced survival of Caenorhabditis elegans infected with fluconazole-resistant C. albicans. The present study indicates 4b warrants further investigation as a novel antifungal agent.

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Discovery and Characterization of Potent Thiazoles versus Methicillin- and Vancomycin-Resistant Staphylococcus aureus

Cited by 96 publications

References 19 publications

Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci

Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant Staphylococci

Identification of tigecycline- and vancomycin-resistant Staphylococcus aureus strains among patients with urinary tract infection in Iran

Discovery of a Novel Dibromoquinoline Compound Exhibiting Potent Antifungal and Antivirulence Activity That Targets Metal Ion Homeostasis

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