Synthesis of 3,5-Bis(trifluoromethyl)phenyl-Substituted Pyrazole Derivatives as Potent Growth Inhibitors of Drug-Resistant Bacteria

Alkhaibari, Ibrahim S.; Kc, Hansa Raj; Roy, Subrata; Abugazleh, Mohd Kotaiba; Gilmore, David F.; Alam, Mohammad A.

doi:10.3390/molecules26165083

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…These studies are very significant, as S. aureus biofilms are very challenging to treat with the existing antibiotics [ 32 ]. Similarly, E. faecalis readily forms biofilms, which are recalcitrant to existing treatments [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

Gilmore

Alam

2022

Antibiotics

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From a library of compounds, 11 hit antibacterial agents have been identified as potent anti-Gram-positive bacterial agents. These pyrazole derivatives are active against two groups of pathogens, staphylococci and enterococci, with minimum inhibitory concentration (MIC) values as low as 0.78 μg/mL. These potent compounds showed bactericidal action, and some were effective at inhibiting and eradicating Staphylococcus aureus and Enterococcus faecalis biofilms. Real-time biofilm inhibition by the potent compounds was studied, by using Bioscreen C. These lead compounds were also very potent against S. aureus persisters as compared to controls, gentamycin and vancomycin. In multiple passage studies, bacteria developed little resistance to these compounds (no more than 2 × MIC). The plausible mode of action of the lead compounds is the permeabilization of the cell membrane determined by flow cytometry and protein leakage assays. With the detailed antimicrobial studies, both in planktonic and biofilm contexts, some of these potent compounds have the potential for further antimicrobial drug development.

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Section: Resultsmentioning

confidence: 99%

Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

Gilmore

Alam

2022

Antibiotics

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“…Following the previously reported protocol, the Calgary biofilm device was used to determine the minimum biofilm eradication concentration (MBEC) of the compounds against two strains of biofilm-forming bacteria . Briefly, biofilm was established on the pegs of the Calgary device by culturing bacterial strains (∼1 × 10 6 CFU/mL) in CAMHB with 1% glucose for 24 h at 35 °C.…”

Section: Methodsmentioning

confidence: 99%

Development and Antibacterial Properties of 4-[4-(Anilinomethyl)-3-phenylpyrazol-1-yl]benzoic Acid Derivatives as Fatty Acid Biosynthesis Inhibitors

Roy,

KC,

Roberts

et al. 2023

J. Med. Chem.

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A number of novel pyrazole derivatives have been synthesized, and several of these compounds are potent antibacterial agents with minimum inhibitory concentrations as low as 0.5 μg/mL. Human cell lines were tolerant to these lead compounds, and they showed negligible hemolytic effects at high concentrations. These bactericidal compounds are very effective against bacterial growth in both planktonic and biofilm contexts. Various techniques were applied to show the inhibition of biofilm growth and eradication of preformed biofilms by lead compounds. Potent compounds are more effective against persisters than positive controls. In vivo studies revealed that lead compounds are effective in rescuing C. elegans from bacterial infections. Several methods were applied to determine the mode of action including membrane permeability assay and SEM micrograph studies. Furthermore, CRISPRi studies led to the determination of these compounds as fatty acid biosynthesis (FAB) inhibitors.

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Thiazole, a privileged scaffold in drug discovery

Alam

2023

Privileged Scaffolds in Drug Discovery

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Synthesis of 3,5-Bis(trifluoromethyl)phenyl-Substituted Pyrazole Derivatives as Potent Growth Inhibitors of Drug-Resistant Bacteria

Cited by 6 publications

References 31 publications

Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

Development and Antibacterial Properties of 4-[4-(Anilinomethyl)-3-phenylpyrazol-1-yl]benzoic Acid Derivatives as Fatty Acid Biosynthesis Inhibitors

Thiazole, a privileged scaffold in drug discovery

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