Minimum inhibitory concentration (MIC in μg/mL) of thiazole compounds 1–5, clindamycin, and mupirocin (tested in triplicate) against five methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and one mupirocin-resistant <i>S</i>. <i>aureus</i> (NRS107) strain isolated from skin wounds.

<p>Minimum inhibitory concentration (MIC in μg/mL) of thiazole compounds 1–5, clindamycin, and mupirocin (tested in triplicate) against five methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and one mupirocin-resistant <i>S</i>. <i>aureus</i> (NRS107) strain isolated from skin wounds.</p

Combination testing of thiazole compounds 1–3 with mupirocin against clinically-prevalent strains of community-acquired methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA).

<p>¹ ƩFIC, fractional inhibitory concentration index. Results for the FIC index (ƩFIC) are as follows: ≤ 0.50, synergistic; >0.50 to ≤4.00, indifference; >4.00, antagonistic. ƩFIC range provided is from two independent experiments.</p><p>Combination testing of thiazole compounds 1–3 with mupirocin against clinically-prevalent strains of community-acquired methicillin-resistant <i>Staphylococcus aureus</i> (CA-MRSA).</p

Toxicity analysis of thiazole compounds against human keratinocytes (HaCaT).

<p>Percent viable mammalian cells (measured as average absorbance ratio (test agent relative to DMSO)) for cytotoxicity analysis of thiazole compounds <b>1</b>, <b>2</b>, <b>3</b>, <b>4</b>, and <b>5</b> (tested in triplicate) at 10 and 20 μg/mL against HaCaT cells using the MTS 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Dimethyl sulfoxide (DMSO) was used as a negative control to determine a baseline measurement for the cytotoxic impact of each compound. The absorbance values represent an average of a minimum of three samples analyzed for each compound. Error bars represent standard deviation values for the absorbance values. A one-way ANOVA, with post hoc Dunnet’s multiple comparisons test, determined statistical difference between the values obtained for compound <b>1</b> and DMSO (denoted by the asterisk) (<i>P</i> < 0.05).</p

Average log₁₀-reduction in MRSA USA300 burden in infected murine skin wounds.

<p>Evaluating the effectiveness of treatment of MRSA skin lesions in mice with mupirocin (2%), thiazole compounds <b>1</b>–<b>5</b> (2%), and compound <b>1</b> (2%, using Lipoderm as the vehicle) twice daily for three days. The average log₁₀-reduction in bacterial burden (relative to the negative control group (petroleum jelly)) was calculated and presented in the figure. Error bars represent standard deviation values. A one-way ANOVA, with post hoc Holm-Sidak’s multiple comparisons test revealed statistical difference (denoted by asterisk) between compounds <b>1</b>, <b>3</b>, <b>4</b>, <b>5</b>, <b>1</b> (using Lipoderm as the vehicle), and mupirocin relative to the negative control (<i>P</i> < 0.05).</p

Drug-resistant clinical isolates of <i>Staphylococcus aureus</i> used in this study.

<p>¹NARSA, Network on Antimicrobial Resistance in <i>Staphylococcus aureus</i>.</p><p>Drug-resistant clinical isolates of <i>Staphylococcus aureus</i> used in this study.</p

Evaluation of toxicity and antimicrobial efficacy of EB in <i>C</i>. <i>elegans</i> model.

<p>(a) <i>C</i>. <i>elegans</i> strain glp-4; sek-1 (L4-stage) were grown for three days in the presence of EB (4μg and 8 μg/ml) and vancomycin (8 μg/ml). Live worms were counted and the results were expressed as percent live worms in relative to the untreated control groups. (b) MRSA USA300 infected L4-stage worms were treated with EB (4μg and 8 μg/ml) and vancomycin (8 μg/ml) for 24 h. Worms were lysed and the CFU were counted and the percent bacterial reduction per worm in treated groups were calculated in relative to the untreated control groups. <i>P</i> values of (** ≤ 0.05) are considered as significant.</p

Cytotoxicity assay in murine macrophage-like cells (J774A.1) cells.

<p>J774A.1 cells were treated with different concentration of EB ranging from 0 to 256 μg/ml. DMSO was used as a negative control. Cell viability was measured by MTS assay and IC₅₀ of EB to cause cytotoxicity in J774A.1 cells was calculated.</p

Effects of EB on coupled transcription-translation (TT) in S30 extracts from <i>E</i>. <i>coli</i>.

<p>(a) Average luciferin protein production in the presence of EB, ampicillin and chloramphenicol at the concentration of 2 μg/ml were shown. The results are given as means ± SD (n = 3). (b) Concentration dependent TT-inhibition of EB and chloramphenicol were shown. IC₅₀ of the drugs required to inhibit 50% TT-activity were determined. <i>P</i> values of (** ≤ 0.05) are considered as significant.</p

Effects of EB on mammalian protein synthesis.

<p>(a) Concentration dependent inhibition of protein synthesis were determined using rabbit reticulocyte lysate extract system. IC₅₀ of the EB required to inhibit 50% translational activity were determined. (b) Effect of EB, chloramphenicol and ampicillin on mitobiogenesis. J774A.1 cell In cell- ELISA was carried out in the presence and absence of these drugs, and the levels of mitochondrial (mt)-DNA encoded protein (COX-I) and nuclear-DNA encoded protein (SDH-A) were quantified. Ratio of COX-I and SDH-A were calculated and the results were shown as percent inhibition of mitochondrial biogenesis.</p

Chemical structures of thiazole compounds 1–5 presented in this study.

<p>Chemical structures of thiazole compounds 1–5 presented in this study.</p