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

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

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

Enterococci and methicillin-resistant S. aureus (MRSA) are among the menacing bacterial pathogens. Novel antibiotics are urgently needed to tackle these antibiotic-resistant bacterial infections. This article reports the design, synthesis, and antimicrobial studies of 30 novel pyrazole derivatives. Most of the synthesized compounds are potent growth inhibitors of planktonic Gram-positive bacteria with minimum inhibitory concertation (MIC) values as low as 0.25 µg/mL. Further studies led to the discovery of several lead compounds, which are bactericidal and potent against MRSA persisters. Compounds 11, 28, and 29 are potent against S. aureus biofilms with minimum biofilm eradication concentration (MBEC) values as low as 1 µg/mL

Enumeration of <i>Dehalococcoides mccartyi</i> in enrichment cultures.

<p>qPCR tracking <i>Dehalococcoides</i> 16S rRNA genes and their reductive dehalogenase genes, <i>tceA</i>, <i>vcrA</i>, and <i>bvcA</i> in the enrichment cultures after three consecutive additions of 0.5 mmol L⁻¹ TCE. The plot is representative of triplicate cultures and the error bars show standard deviations of triplicate qPCR reactions.</p

Environmental inocula and enrichment conditions of chlorinated ethene-dechlorinating cultures.

<p>Enrichment originating <i>Dehalococcoides mccartyi</i> strain ^a195, ^bBAV1, ^cVS, and ^dFL2.</p

Bioaugmentation of microcosms with their respective enrichment cultures.

<p>Dechlorination of TCE in (A) in Cuzdrioara soil microcosms bioaugmentated with ZARA-10 enrichment culture and in (B) Carolina sediment microcosms bioaugmented with LINA-09 culture. The inoculum used for these experiments was 1% vol/vol.</p

Alpha and beta microbial diversity analyses.

<p>(A)–(C) Rarefaction plots for PD Whole Tree measurements from the 454 analysis using trimmed, equal sequencing depth OTUs (1,486) per sample. (D) Weighted UNIFRAC distance calculated after trimming the samples to equal sequence depth in QIIME. The PCoA plot was generated by grouping the samples into two categories (soils/sediments vs. enrichment cultures). The color blue corresponds to the soil/sediment samples, while green corresponds to the soil/sediment-free enrichment cultures.</p