An exploration of optimal time and safety of 595-nm pulsed dye laser for the treatment of early superficial infantile hemangioma.

Infantile hemangioma (IH) is the most common benign vascular tumor that occurs in infants and young children. Studies have shown laser therapy to reduce the proliferation of superficial IH and promote its regression, but the optimal timing for treatment has not been determined. Our study explores the timing and safety of 595-nm pulsed dye laser (PDL) treatment for early superficial IH. We retrospectively analyzed 180 cases of superficial IH treated with 595-nm PDL. Data was organized according to patient age at the first visit. Six months after the initial treatment, patients were evaluated using a grade IV classification method, and the clinical curative effect of each group was calculated. The number of laser treatments and the occurrence of adverse reactions were recorded simultaneously. The overall effective and cure rates were 98.3% and 84.4%, respectively, with no significant difference in rates between groups (p > 0.05). There was a statistically significant difference in the number of laser treatments among the age groups (p < 0.05). The average laser frequency: "0-2 months group" < "2-4 months group" < "4-6 months group." The overall incidence of adverse reactions was 11.1%, and 12 (6.7%) cases had short-term adverse reactions, with no statistically significant differences between groups (p > 0.05). Eight cases had long-term adverse reactions. This difference between groups was statistically significant (p < 0.05). Younger children (≤2 months of age) receiving 595-nm PDL treatment for IH require relatively fewer treatment times than other children (>2 months of age), have a shorter course of disease, experience better curative effect, and have fewer sequelae reactions.

Arylamino containing hydroxamic acids as potent urease inhibitors for the treatment of Helicobacter pylori infection.

A novel series of aniline-containing hydroxamic acids were designed, synthesized and evaluated as anti-virulence agents for the treatment of gastritis and gastric ulcer caused by Helicobacter pylori. In vitro enzyme-based screen together with in vivo assays and structure-activity relationship (SAR) studies led to the discovery of three potent urease inhibitors 3-(3,5-dichlorophenylamino)N-hydroxypropanamide (3a), 3-(2-chlorophenylamino)N-hydroxypropanamide (3d) and 3-(2,4-dichlorophenylamino)N-hydroxypropanamide (3n). Compounds 3a, 3d and 3n showed excellent urease inhibition with IC50 values 0.043 ±â€¯0.005, 0.055 ±â€¯0.008 and 0.018 ±â€¯0.002 µM, and significantly depressed gastritis developing at the dose of 32 mg/kg b. i.d with eradication rates of H. pylori reaching 92.3, 84.6 and 100%, respectively. Preliminary safety studies (acute toxicity in mice) disclosed that 3a, 3d and 3n was well-tolerated in KM mice with LD50s of 2982.8, 3349.4 and 3126.9 mg/kg, respectively. Collectively, the data obtained in this study indicate that 3a, 3d and 3n, in particular 3n, could considered as promising candidates for the potential treatment of H. pylori caused gastritis and gastric ulcer, and hence merit further studies.

Synthesis and evaluation of adenosine containing 3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors.

Tyrosyl-tRNA synthetase (TyrRS) is an aminoacyl-tRNA synthetase family protein that possesses an essential role in bacterial protein synthesis. The synthesis, structure-activity relationship, and evolution of a novel series of adenosine-containing 3-arylfuran-2(5H)-ones as TyrRS inhibitors are described. Advanced compound d3 from this series exhibited excellent affinity for TyrRS with IC50 of 0.61 ± 0.04 µM. Bacterial growth inhibition assays demonstrated that d3 showed submicromolar antibacterial potency against Escherichia coli and Pseudomonas aeruginosa, and compared to the marketed antibiotics ciprofloxacin.

3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation.

Helicobacter pylori urease is involved in several physiologic responses such as stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus, inhibition of urease is taken for a good chance to treat H. pylori-caused infections, we have therefore focused our efforts on seeking novel urease inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5-chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active inhibitor with IC50 of 0.15±0.05µM, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12µg·mL(-1) for Ki and Ki', respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins.

Adenosine analogs as inhibitors of tyrosyl-tRNA synthetase: Design, synthesis and antibacterial evaluation.

Herein we describe the synthesis and evaluation of a series of adenosine analogs for in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Out of these compounds, compound c6 has much stronger antibacterial potency against Pseudomonas aeruginosa than ciprofloxacin, and was determined to target tyrosyl-tRNA synthetase with IC50 of 0.8±0.07 µM. Structure-activity relationship analysis suggested that introduction of a fluorine atom at the 3'-position of benzene ring of the phenylacetyl moiety significantly increased affinities to the enzyme. In comparison with isopropylidene analogs, 2',3'-deprotected compounds displayed higher inhibitory activity. Molecular dockings provided an explanation for observations in biological assays.

Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold.

Tyrosyl-tRNA synthetase (TyrRS), an essential enzyme in bacterial protein biosynthesis, is an attractive therapeutic target for finding novel antibacterial agents, and a series of N2-(arylacetyl)glycinanilides has been herein synthesized and identified as TyrRS inhibitors. These efforts yielded several compounds, with IC50 in the low micromolar range against TyrRS from Staphylococcus aureus. Out of the obtained compounds, 3ap is the most active and exhibits excellent activity against both Gram-positive (S. aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. In comparison with the parent scaffold 3-arylfuran-2(5H)-one, N2-(arylacetyl)glycinanilide significantly improved the potency against Gram-negative bacterial strains, indicating that this scaffold offers a significant potential for developing new antibacterial drugs.

Synthesis and evaluation of N-analogs of 1,2-diarylethane as Helicobacter pylori urease inhibitors.

Therapies based on urease inhibition are now seriously considered as the first line of treatment for infections caused by Helicobacter pylori. However, the present inhibitors are ineffective or unstable in highly acidic gastric juice. Here, we report a series of benzylanilines as effective inhibitors of H. pylori urease. Out of the obtained twenty-one compounds, N-(3,4-dihydroxybenzyl)-4-nitroaniline (4) was evaluated in detail and shows promising features for development as anti-H. pylori agent. Excellent potency against urease in both cell-free extract and intact cell was observed at low concentrations of 4 (IC50=0.62 ± 0.04 and 1.92 ± 0.09 µM), which showed over 29- and 54-fold increase in potency with respect to the positive control AHA. The SAR analysis revealed that protection of 3,4-dihydroxy group of 4 as methoxy or changes of 4-NO2 will result in a moderate to dramatic decrease in potency.

Synthesis, molecular docking and biological evaluation of 3-arylfuran-2(5H)-ones as anti-gastric ulcer agent.

3-Arylfuran-2(5H)-one derivatives show good antibacterial activity and were determined as tyrosyl-tRNA synthetase (TyrRS) inhibitors. In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to treat infections caused by Helicobacter pylori. Twenty 3-arylfuran-2(5H)-ones were synthesized and evaluated for anti-H. pylori, antioxidant and anti-urease activities which are closely interconnected with H. pylori infection. The results displayed that some of the compounds show excellent antioxidant activity, and good anti-H. pylori and urease inhibitory activities. Out of these compounds, 3-(3-methylphenyl)furan-2(5H)-one (b9) showed the most potent antioxidant activity (IC50=8.2 µM) and good anti-H. pylori activity (MIC50=2.6 µg/mL), and it can be used as a good candidate for discovering novel anti-gastric ulcer agent.