Design, Synthesis, and Biological Evaluation of 2‑Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 μg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 μg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect

Design, Synthesis, and Biological Evaluation of 2‑Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 μg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 μg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect

Design, Synthesis, and Biological Evaluation of 2‑Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 μg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 μg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect

Design, Synthesis, and Biological Evaluation of 2‑Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 μg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 μg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect

Design, Synthesis, and Biological Evaluation of 2‑Phenoxyalkylhydrazide Benzoxazole Derivatives as Quorum Sensing Inhibitors with Strong Antibiofilm Effect

With the increasing problem of bacterial resistance to traditional antibiotics, there is an urgent need for new antibacterial agents with novel mechanisms to treat infections caused by drug-resistant bacteria. In this paper, we designed and synthesized 2-phenoxyalkylhydrazide benzoxazole derivatives and evaluated their quorum sensing inhibition activity. Among them, 26c at a concentration of 102.4 μg/mL not only inhibited the production of pyocyanin and rhamnolipid by 45.6% and 38.3%, respectively, but also suppressed 76.6% of biofilm production at 32 μg/mL. In addition, 26c did not affect bacterial growth, but in a mouse model infected with P. aeruginosa PAO1, it could help ciprofloxacin effectively eliminate the living bacteria. In the targeting experiment, 26c could inhibit the fluorescence intensity of PAO1-lasB-gfp and PAO1-pqsA-gfp in a concentration-dependent manner, indicating that the compound acts on the quorum sensing system. Overall, 26c is worthy of further investigation as a quorum sensing inhibitor with strong antibiofilm effect

YAP is significantly upregulated in human ovarian cancer tissues and is associated with patient prognosis.

<p><b>A</b>: Immunohistochemistry results for YAP and pYAP expression in normal human ovary tissues and four subtypes of ovarian cancer tissue. Sections were counterstained with hematoxylin. Magnifications at 40× and 100× are shown. Scale bar  = 100 μM for all panels. <b>B</b>: Kaplan-Meier analysis for associations between YAP expression, localization, and phosphorylation and ovarian cancer patient survival. P-values are from log-rank tests.</p

High YAP and TEAD4 co-expression levels are associated with a poor prognosis with primary human ovarian cancers.

<p><b>A</b>. IHC results for TEADs expression in human ovarian cancer tissues. Scale bar  = 100 μM. <b>B</b>. Associations between YAP/pYAP expressions and TEAD expressions in an ovarian cancer tissue array. <b>C</b>. Associations between YAP and TEAD4 expressions in 45 ovarian cancer samples ranked by Kaplan-Meier survival estimates. <b>D</b>. YAP and TEAD4 co-expression is associated with a poor prognosis with human ovarian cancer. High TEAD expression versus low TEAD4 expression (left), high YAP expression combined with high TEAD4 expression versus other categories (middle), high YAP expression and high TEAD4 expression combined with high β-catanin versus other categories (right).</p

Overexpression of <i>NDRG2</i> suppresses human bladder cancer cell invasion, migration and expression of MMP-2 and MMP-9.

<p>(A) Invasion analysis of T24 cells treated with LEN-<i>NDRG2</i>. The invasion ability was estimated using Transwell coated with Matrigel. The invasiveness of LEN-<i>NDRG2</i> group cells was significantly lower than that in the other two groups. **p<0.001. (B) Migration analysis of T24 cells treated with LEN-<i>NDRG2</i>. The migration ability was estimated using Transwell uncoated with Matrigel. The migration ability of LEN-<i>NDRG2</i> group cells was significantly lower than that in the other two groups. **p<0.001. (C and D) Expression of MMP-2 and MMP-9 were measured after T24 cells were infected with LEN-<i>NDRG2</i>. LEN-<i>NDRG2</i> group reduced MMP-2 and MMP-9 expression compared to the other groups (** p<0.01).</p

The influences of <i>NDRG2</i> overexpression on T24 cells infected with lentivirus.

<p>(A) The effect of <i>NDRG2</i> overexpression on G1 cell cycle and apoptosis regulators as assayed by western blot. (B) Relative quantification of protein expression, normalized to GAPDH levels. The figure shows the tendency of each group as indicated. All the assays were repeated independently for at least three times. The results are shown as the mean ± SD (** p<0.01)..</p

FCA of cell cycle arrest and apoptosis induced by overexpression of <i>NDRG2</i>.

<p>(A) T24cells infected with LEN-<i>NDRG2</i> lentivirus were more obviously arrested in G0/G1cycle. (B) Percentages of apoptotic cells in LEN-<i>NDRG2</i> groups were greater than in the other two groups(1–3). 48 h after the infection (4–6); 72 h after the infection; (1 and 4) blank control (PBS); (2 and 5) LEN-LacZ; (3 and 6) LEN-<i>NDRG2</i>. All the assays were repeated independently for at least three times. The results are shown as the mean ± SD.</p