Microwave-induced CAN promoted atom-economic synthesis of 1H-benzo[b]xanthene and 4H-benzo[g]chromene derivatives of N-allyl quinolone and their antimicrobial activity

Some new 1H-benzo[b]xanthene and 4H-benzo[g]chromene derivatives of N-allyl quinolone were efficiently synthesized via microwave-induced one-pot three component reaction of N-allyl quinolones, 2-hydroxy-1,4-naphthoquinone and cyclic β-diketones/malononitrile, and iso-propylcyanoacetate in the presence of catalytic amount of ceric ammonium nitrate under solvent-free condition. This methodology allowed us to achieve the desired products in excellent yields in a very short time without the use of solvent. The % atom economy was calculated for all the newly synthesized compounds and found in the range of 92–96 %. Titled derivatives were elucidated by ¹H NMR, ¹³C NMR, FT-IR, elemental analysis, and mass spectral data as well as tested against a panel of pathogenic strains of bacteria and fungi using by microdilution minimum inhibitory concentration method. The structural activity relationship analysis demonstrated that electronic influence and lipophilicity of different groups make much difference in the antimicrobial potency.     

Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Platelet Count and Plateletcrit (PCT) as predictors of in-hospital paediatric mortality: a case-control Study

BackgroundThrombocytopenia has been shown to predict mortality. We hypothesize that platelet indices may be more useful prognostic indicators. Our study subjects were children one month to 14 years old admitted to our hospital.AimTo determine whether platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) and their ratios can predict mortality in hospitalised children.MethodsChildren who died during hospital stay were the cases. Controls were age matched children admitted contemporaneously. The first blood sample after admission was used for analysis. Receiver operating characteristic (ROC) curve was used to identify the best threshold for measured variables and the ratios studied. Multiple regression analysis was done to identify independent predictors of mortality.ResultsForty cases and forty controls were studied. Platelet count, PCT and the ratios of MPV/Platelet count, MPV/PCT, PDW/Platelet count, PDW/PCT and MPV × PDW/Platelet count × PCT were significantly different among children who survived compared to those who died. On multiple regression analysis the ratio of MPV/PCT, PDW/Platelet count and MPV/Platelet count were risk factors for mortality with an odds ratio of 4.31(95% CI, 1.69–10.99), 3.86 (95% CI, 1.53–9.75), 3.45 (95% CI, 1.38–8.64) respectively. In 67% of the patients who died MPV/PCT ratio was above 41.8 and PDW/Platelet count was above 3.86. In 65% of patients who died MPV/Platelet count was above 3.45.ConclusionThe MPV/PCT, PDW/Platelet count and MPV/Platelet count, in the first sample after admission in this case control study were predictors of mortality and could predict 65% to 67% of deaths accurately.     

HJP272, A Novel Endothelin Receptor Antagonist,Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Hamsters

Introduction

Previous studies from this laboratory indicate that endothelin-1 (ET-1), a potent vasoconstrictor, may play an important role in lipopolysaccharide (LPS)-induced release of neutrophils from the pulmonary microvasculature. To further test this concept, Syrian hamsters were treated with a novel endothelin receptor A (ETA) antagonist (HJP272) prior to intratracheal instillation of LPS.

Methods

The effect of HJP272 on the LPS-induced inflammatory reaction was determined by measuring: (1) lung histopathological changes, (2) total neutrophils in bronchoalveolar lavage fluid (BALF), (3) expression of tumor necrosis factor receptor 1 (TNFR1) by BALF macrophages, and (4) alveolar septal cell apoptosis.

Results

Treatment with HJP272 significantly reduced each of these parameters during a 24-hr period following LPS instillation, supporting the concept that limiting the activity of ET-1 may reduce the extent of lung injury. This hypothesis was further tested by giving ET-1 prior to LPS instillation, which resulted in a marked enhancement of LPS-induced lung inflammation, as measured by BALF neutrophils and TNFR1-positive macrophages. Furthermore, the increase in neutrophils resulting from treatment with ET-1 was significantly reduced by HJP272, again demonstrating the ability of ETA receptor antagonists to limit the influx of these cells into the lung.

Conclusions

These findings suggest a potential therapeutic role for these agents in diseases where neutrophils are a significant cause of lung injury, such as bronchopneumonia, respiratory distress syndrome, and chronic obstructive pulmonary disease.     

Role for immune monitoring to tailor induction prophylaxis in pediatric heart recipients

rATG is used for HTx induction but is costly and associated with infection and PTLD. Hypothesis: Tailoring rATG induction with CD3 monitoring results in less infection, reduced costs, and similar rejection. Retrospective review of HTx recipients receiving rATG induction. Control cases received “usual” rATG dosing (1.5 mg/kg/day typically × 5 days). Starting in October 2009, absolute CD3 monitoring (target <25 cells/mm³) guided rATG dosing (study cases). Outcomes included first‐year incidence of infection/rejection, direct costs of therapy, and incidence of PTLD/death. Study cases (n = 32) received fewer doses of rATG (median 4 vs. 5, p < 0.001) and less total rATG (median 3.2 vs. 7.4 mg/kg, p < 0.001) compared with controls (n = 17). There was no difference in incidence of infection, rejection, or patient survival during the first year post‐HTx. There was one early death in both groups and one late case of PTLD in the control group. Drug savings were significant (median drug cost per patient $2718 vs. $4756, p < 0.001). CD3‐tailored rATG induction in HTx recipients is associated with reduced drug costs and similar rates of rejection/infection. Longer follow‐up will determine whether extended benefits are associated with this induction monitoring strategy.     

Microwave-irradiated synthesis and antimicrobial activity of 2-phenyl-7-substitutedalkyl/arylaminoquinoline-4-carboxylic acid derivatives

This report focuses on the synthesis of 2-phenyl-7-substitutedquinoline-4-carboxylic acid derivatives through both conventional and microwave-irradiated methods. Intermediate 7-chloro-2-phenyl-quinoline-4-carboxylic acid was synthesized by condensation and cyclization of benzaldehyde, pyruvic acid, and m-chloroaniline in the presence of absolute ethanol and further substituted with aromatic, aliphatic, and alicyclic amines to obtain the desired 2-phenyl-7-substitutedaryl/alkylamino-quinoline-4-carboxylic acid derivatives under the influence of microwave irradiation, with output power ranging from 160 to 480 W, yield ranging from 90% to 95%, and a shorter reaction time than with the conventional method. All the synthesized compounds were screened for in vitro antimicrobial activity against six gram-positive and four gram-negative organisms. All synthesized compounds are active against a broad spectrum of microorganisms, with prominent results for Streptococcus pyrogenes and Pseudomonas aeruginosa. Compounds 7c and 7h showed a minimum inhibitory concentration of less than 10 μg.