4-Diazopyrazole Derivatives as Potential New Antibiofilm Agents

Schillaci, Domenico; Maggio, Benedetta; Raffa, Demetrio; Daidone, Giuseppe; Cascioferro, Stella; Cusimano, Maria Grazia; Raimondi, Maria Valeria

doi:10.1159/000159271

Cited by 15 publications

(10 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Quorum-sensing phenomenon, which is one of the ways to control biofilms, is a chemical form of bacterial communication via signaling molecules essential for bacterial communities to regulate the group and to synchronize the behavior (Hastings and Greenberg, 1999; Van Houdt et al , 2004; Raffa et al , 2005; Waters and Bassler, 2005; Musk and Hergenrother, 2006; Bjarnsholt and Givskov, 2007; Amer et al , 2008; Labandeira-Rey et al , 2009; Deep et al , 2011). In agreement with the data provided by the literature, pyrazole compounds may act as inhibitors that target this cell–cell signaling mechanism (Tanitame et al , 2004; Musk and Hergenrother, 2006; Tse-Dinh, 2007; Schillaci et al , 2008; Brackman et al , 2009; Oancea, 2010). The number of literature data dealing with regulatory mechanisms controlling the haemophili biofilm formation and a possible effect of different chemical compounds on this process is strongly limited.…”

Section: Resultssupporting

confidence: 84%

“…Considering a possible mechanism of anti-biofilm activity of N -ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1 H -pyrazole-1-carbothioamide, it should be noted that several classes of chemical compounds, e.g., pyrazole or thioamide derivatives, may act as quorum-sensing inhibitors (Hentzer and Givskov, 2003; Schillaci et al 2008; Brackman et al , 2009; Kociolek, 2009; Oancea, 2010). Quorum-sensing phenomenon, which is one of the ways to control biofilms, is a chemical form of bacterial communication via signaling molecules essential for bacterial communities to regulate the group and to synchronize the behavior (Hastings and Greenberg, 1999; Van Houdt et al , 2004; Raffa et al , 2005; Waters and Bassler, 2005; Musk and Hergenrother, 2006; Bjarnsholt and Givskov, 2007; Amer et al , 2008; Labandeira-Rey et al , 2009; Deep et al , 2011).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

et al. 2013

View full text Add to dashboard Cite

During this study, we have investigated in vitro activity of N-substituted-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide derivatives with N-ethyl, N-(4-metoxyphenyl) and N-cyclohexyl substituents against Gram-negative Haemophilus influenzae and H. parainfluenzae bacteria. A spectrophotometric assay was used in order to determine the bacterial growth and biofilm formation using a microtiter plate to estimate minimal inhibitory concentration (MIC) and minimal biofilm inhibitory concentration (MBIC). Among the tested N-substituted pyrazole derivatives, only N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide showed a significant in vitro activity against both planktonic cells of H. parainfluenzae (MIC = 0.49–31.25 μg ml−1) and H. influenzae (MIC = 0.24–31.25 μg ml−1) as well as biofilm-forming cells of H. parainfluenzae (MBIC = 0.24–31.25 μg ml−1) and H. influenzae (MBIC = 0.49 to ≥31.25 μg ml−1). The pyrazole compound exerted higher inhibitory effect both on the growth of planktonic cells and biofilm formation by penicillinase-positive and penicillinase-negative isolates of H. parainfluenzae than the activity of commonly used antibiotics such as ampicillin. No cytotoxicity of the tested compound in vitro at concentrations used was found. The tested pyrazole N-ethyl derivative could be considered as a compound for the design of agents active against both pathogenic H. influenzae and opportunistic H. parainfluenzae, showing also anti-biofilm activity. This appears important because biofilms are determinants of bacterial persistence in long-term and recurrent infections recalcitrant to standard therapy.

show abstract

Section: Resultssupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

et al. 2013

View full text Add to dashboard Cite

show abstract

“…Extended intracellular residency, if demonstrated in other glycopeptide-intermediate isolates of MRSA, would confer a significant fitness benefit to those resistant isolates and thus contribute to their persistence in some clinical situations, especially in the presence of cell wallactive antibiotics whose intracellular activity is limited. In conclusion, the multi-resistance pattern of MRSA is an incentive for the development of novel antimicrobial agents [43,44] .…”

Section: Discussionmentioning

confidence: 99%

Increased Uptake and Improved Intracellular Survival of a Teicoplanin-Resistant Mutant of Methicillin-Resistant <i>Staphylococcus aureus</i> in Non-Professional Phagocytes

et al. 2009

View full text Add to dashboard Cite

Background/Aims: Endogenous development of glycopeptide-intermediate resistance is linked to multiple genetic and phenotypic changes in clinical and laboratory isolates of Staphylococcus aureus. This study evaluated endocytic uptake and intracellular survival of a teicoplanin-resistant derivative of S. aureus in a human epithelial cell line, and compared these to the isogenic teicoplanin-susceptible parent or a spontaneously derived, susceptible revertant. Methods: Endocytic uptake of teicoplanin-resistant and teicoplanin-susceptible strains by human embryonic kidney 293 cells was estimated by a lysostaphin protection assay. Differential intracellular survival of all S. aureus strains from 2 to 24 h was evaluated by colony-forming unit counts of Triton X-100-lysed 293 cells, following lysostaphin inactivation. Results: Endocytic uptake of the teicoplanin-resistant strain increased by approximately 4-fold over its teicoplanin-susceptible counterparts. Furthermore, the teicoplanin-resistant strain showed an 11-fold increase in intracellular colony-forming unit counts from 2 to 24 h, compared to its teicoplanin-susceptible counterparts that showed marginal (<2-fold) changes during the same time period. Infected host cells showed no significant viability loss at 24 h, as assessed by Trypan blue dye exclusion. Conclusions: Intracellular location might confer a significant fitness benefit to glycopeptide-intermediate isolates of methicillin-resistant S. aureus and further protect them from cell wall-active antibiotics whose intracellular activity is limited.

show abstract

“…MICs against planktonic strains were evaluated by a micromethod previously reported (Schillaci et al 2008). Briefly, a series of solution in Tryptic Soy Broth (TSB) with concentrations ranging from 25 to 0.3 mg/ml were obtained by twofold serial dilution in 96 well plate.…”

Section: Minimum Inhibitory Concentrations (Mic)mentioning

confidence: 99%

A peptide from human β thymosin as a platform for the development of new anti-biofilm agents for Staphylococcus spp. and Pseudomonas aeruginosa

Schillaci

Spinello

Cusimano

et al. 2016

World J Microbiol Biotechnol

Self Cite

View full text Add to dashboard Cite

Conventional antibiotics might fail in the treatment of biofilm-associated infections causing infection recurrence and chronicity. The search for antimicrobial peptides has been performed with the aim to discover novel anti-infective agents active on pathogens in both planktonic and biofilm associated forms. The fragment 9-19 of human thymosin β4 was studied through 1 μs MD simulation. Two main conformations of the peptide were detected, both constituted by a central hydrophobic core and by the presence of peripheral charged residues suggesting a possible mechanism of interaction with two models of biological membranes, related to eukaryotic or bacterial membrane respectively. In addition, the peptide was chemically synthesized and its antimicrobial activity was tested in vitro against planktonic and biofilm form of a group of reference strains of Staphylococcus spp. and one P. aeruginosa strain. The human thymosin β4 fragment EIEKFDKSKLK showed antibacterial activity against staphylococcal strains and Pseudomonas aeruginosa ATCC 15442 at concentrations from 12.5 to 6.2 mg/ml and inhibited biofilm formation at sub-inhibitory concentrations (3.1-0.75 mg/ml). The activity of the fragment in inhibiting biofilm formation, could be due to the conformations highlighted by the MD simulations, suggesting its interaction with the bacterial membrane. Human thymosin β4 fragment can be considered a promising lead compound to develop novel synthetic or recombinant derivatives with improved pharmaceutical potential.

show abstract

4-Diazopyrazole Derivatives as Potential New Antibiofilm Agents

Cited by 15 publications

References 30 publications

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

Inhibitory effect of N-ethyl-3-amino-5-oxo-4-phenyl-2,5-dihydro-1H-pyrazole-1-carbothioamide on Haemophilus spp. planktonic or biofilm-forming cells

Increased Uptake and Improved Intracellular Survival of a Teicoplanin-Resistant Mutant of Methicillin-Resistant <i>Staphylococcus aureus</i> in Non-Professional Phagocytes

A peptide from human β thymosin as a platform for the development of new anti-biofilm agents for Staphylococcus spp. and Pseudomonas aeruginosa

Contact Info

Product

Resources

About