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A series of amides was synthesized by coupling of 3-aminomethylglaucine with various amino acid analogues. The reaction was carried out under mild conditions by using various carbodiimides and in the presence of catalytic amount of N-hydroxybenzotriazole. Five of the compounds obtained were new, and their spectral data are presented and discussed here. Selected amides were tested for their ability to scavenge the stable free 1,1-diphenyl-2-picryl-hydrazyl (DPPH●) radical. The most active compounds were N-sinapoylphenylalanyl-3-aminomethylglaucine amide and N-feruloylphenylalanyl-3-aminomethylglaucine amide and their activity was due to the presence of hydroxycinnamoyl moiety in their molecules. The compounds were further tested in vitro for antiviral activity against viruses belonging to the Picornaviridae family. Furthermore, anti-tyrosinase activity of the compounds was performed in vitro. The results obtained suggested that the most promising tyrosinase inhibitor was feruloylphenylalanyl-3-aminomethylglaucine [ABSTRACT FROM AUTHOR]

A series of 4-(substituted benzylidene-amino)-2,3-dimethyl-1-phenyl- 3-pyrazoline-5-ones (3a-l) was obtained using sonochemical assisted reaction. The synthesized Schiff bases were evaluated for their antiviral, antibacterial, anticandida, DPPH scavenging and anti-tyrosinase activities in vitro. The antimicrobial screening results revealed that amongst the tested imines, compound 3l appeared to be а promising one (with a minimal inhibitory concentration 47 ug/ml). The most potent DPPH scavengers were azometines 3a and 3g. No significant inhibition on the monophenolase activity in vitro of mushroom tyrosinase was observed. [ABSTRACT FROM AUTHOR]

N -phenylpropenoyl amino acid amides have been brominated using two alternative sonochemically activated green chemistry procedures. The first synthetic procedure has involved an ultrasound assisted bromination in an aqueous medium using ionic liquid as a catalyst of the reaction, whereas in the second one an in situ formation of Br 2 via oxidation of HBr by H 2 O 2 has been used. For comparison, the conventional bromination procedure was also used. The newly brominated compounds were characterized by appropriate analytical techniques. A detailed NMR spectroscopic analysis and quantum chemical calculations using Density Functional Theory (DFT) methods have been used to define the stereochemistry of the products. The results confirmed the physicochemical identity and similar yields of the products obtained by the three synthetic procedures employed, and reveal the co-existence of two diastereoisomeric forms of the newly synthesized products. The antibacterial and antifungal activities of the dibrominated amides were evaluated. [ABSTRACT FROM AUTHOR]

The emergence of a novel pandemic influenza A (H1N1) strain in 2009 is an evident mark for the unremitting risk of respiratory viral diseases. Influenza outbreaks and development of desease and could be overcome by use of vaccines and antivirals. Currently, clinically applied influenza antivirals are limited to M2 ion channel blockers (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir). Development of resistant viral progeny though, is one of the major challenges to antiviral chemotherapy, in general. Resistant viral mutants are described to both classes of anti-influenza antivirals, as well. Therefore, the development of new antiviral agents for influenza treatment is a hot topic and a never ending task. Combining antiviral drugs with antioxidants in severe influenza-associated complications is of great therapeutic significance. Based on the prominent antioxidant activity of hydroxycinnamic acids, herein, we report the biological activity of newly synthesized amides obtained by coupling previously synthesized N-hydroxycinnamoyl amides of fluorinated amino acids and a fragment of oseltamivir. [ABSTRACT FROM AUTHOR]

Highlights: [•] Eight N-hydroxycinnamoylamides of fluorinated amino acids have been synthesized, among them five are new. [•] We evaluated their antioxidative activities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test. [•] Among the tested amides, N-sinapoyl-3-fluorotyrosine methyl ester (5) exhibited the highest radical-scavenging activity. [•] SA-Trp(6-F)-OMe (4) inhibited the most significantly the formation of dopachrome in anti-tyrosinase assay. [ABSTRACT FROM AUTHOR]

Abstract Objectives The impact of economic evaluation studies on health-care decision makers has been shown to be rather limited. However, there is an increasing requirement for the cost-effectiveness of health-care interventions to be considered in formulating and implementing guidelines for clinical practice. This paper reports the findings of recent focus group research among UK health authorities, which examined the usefulness of published economic evaluations within the decision-making processes. The findings are presented and discussed in light of other studies that have addressed this issue. Methods Focus group research was conducted with decision makers from a sample of two UK health authorities using the National Health Service Economic Evaluation Database (NHS EED) as a research vehicle to locate and report the findings of relevant economic studies. The study sample was initially invited to respond to questionnaires exploring the usefulness of published economic evaluations in the decision-making process and to outline particular topics that it felt would benefit from similar economic evidence. Following this, a detailed search was undertaken to retrieve structured NHS EED abstracts on these topics such that the usefulness and limitations of economic evaluations to decision making could be determined. Results Decision makers generally recognized the usefulness and necessity of published economic evaluations in informing their decision-making processes. However, the value of studies was often limited because of the poor generalizability of results, the narrowness of research questions, and the lack of methodological rigor common to many published studies. A total of 237 NHS EED full abstracts were retrieved in the specified areas of interest, which, within specified caveats, were generally found to be useful as decision-making tools. There was a general consensus among decision makers in favor of developing a quality-scoring system for studies, thereby... [ABSTRACT FROM AUTHOR]

Focuses on the decision-making in the National Health Service (NHS) in Great Britain. Use of economic evaluation in medical care decision-making; Clinical development plans for drugs; Reorganizations in NHS.

Currently, there is an increasing interest towards α-glucosidase inhibition of various diseases including diabetes mellitus type 2, cancer, HIV, and B- and C-type viral hepatitis. Cinnamic acid derivatives have been shown to be potentially valuable as a new group of α-glucosidase inhibitors. Therefore, herein, the α-glucosidase inhibitory activity of trans-N-cinnamoyl and hydroxycinnamoyl amides was studied in vitro. Results revealed that the tested hydroxycinnamoyl amides (1–16) inhibited a-glucosidase with IC50s ranging between 0.76 and 355.1 μg/ml. Compounds 1, 2, 5, 6, 9, 14, and 15 showed significant inhibition of yeast α-glucosidase, being even more potent ones than the used positive inhibitor acarbose (IC50=2.50±0.21 μg/ml). [ABSTRACT FROM AUTHOR]

Discusses the importance of information on cost effectiveness in health care. Role of the National Health Service (NHS) Economic Evaluation Database (EED) project in Great Britain; Database of studies on economic evaluations, which has been compiled by the project; Goal of the project being to assist researchers and decision makers in identifying and interpreting economic evaluations.

Summary: Background: Testing for human papillomavirus (HPV) DNA is reportedly more sensitive than cytology for the detection of high-grade cervical intraepithelial neoplasia (CIN). The effectiveness of HPV testing in primary cervical screening was assessed in the ARTISTIC trial, which was done over two screening rounds approximately 3 years apart (2001–03 and 2004–07) by comparing liquid-based cytology (LBC) combined with HPV testing against LBC alone. Methods: Women aged 20–64 years who were undergoing routine screening as part of the English National Health Service Cervical Screening Programme in Greater Manchester were randomly assigned (between July, 2001, and September, 2003) in a ratio of 3:1 to either combined LBC and HPV testing in which the results were revealed and acted on, or to combined LBC and HPV testing where the HPV result was concealed from the patient and investigator. The primary outcome was the detection rate of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in the second screening round, analysed by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821. Findings: There were 24 510 eligible women at entry (18 386 in the revealed group, 6124 in the concealed group). In the first round of screening 233 women (1·27%) in the revealed group had CIN3+, compared with 80 (1·31%) women in the concealed group (odds ratio [OR] 0·97, 95% CI 0·75–1·25; p>0·2). There was an unexpectedly large drop in the proportion of women with CIN3+ between the first and second rounds of screening in both groups, at 0·25% (29 of 11 676) in the revealed group and 0·47% (18 of 3866 women) in the concealed group (OR 0·53, 95% CI 0·30–0·96; p=0·042). For both rounds combined, the proportion of women with CIN3+ were 1·51% (revealed) and 1·77% (concealed) (OR 0·85, 95% CI 0·67–1·08; p>0·2). Interpretation: LBC combined with HPV testing resulted in a significantly lower detection rate of CIN3+ in the second round of screening compared with LBC screening alone, but the effect was small. Over the two screening rounds combined, co-testing did not detect a higher rate of CIN3+ or CIN2+ than LBC alone. Potential changes in screening methodology should be assessed over at least two screening rounds. Funding: National Institute of Health Research Health Technology Assessment Programme. [Copyright &y& Elsevier]

• Novel memantine hybrids based on cinnamic skeleton were synthesiszed. • The X-ray crystal structures of memantine hybrids 2–5 were provided. • N -sinapoylamide of memantine (3) was the most active antioxidant in the applied in vitro radical scavenging tests. • Synthetically obtained memantine hybrids can be considered as promising neuroprotective agents in vitro. Herein, framework combinations of antioxidant substituted cinnamic acids and memantine (N -methyl- d -aspartate receptor antagonist) in a new multi-targeted chemical entity were described. The amide bond formation of the memantine hybrids 1–5 was performed by EDC/HOBt coupling reaction. The chemical structures of the synthesized compounds were confirmed by means of melting points, UV, IR, 1H NMR, 13C NMR, and HRMS. Additionally, the crystal structures of memantine hybrids (2–5) were also studied by single-crystal X-ray diffraction. The single-crystal X-ray analysis revealed that the compounds 2, 5 crystallize in a centrosymmetric manner both in monoclinic space group (SG) P 2 1 /c, (No 14) and in a non-centrosymmetric manner for compounds 3 and 4, SG R 3, (No 146) and SG P 2 1 2 1 2 1 , (No 19), respectively. Furthermore, preliminary in vitro screenings of their neuroprotective and radical scavenging activities were performed. The radical scavenging activity of synthesized memantine hybrids was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH●), hydroxyl (OH●) and superoxide (O2●▬) radicals and compared with the standard antioxidants (ferulic and sinapic acids). Radical scavenging activity studies show that amongst the tested hybrids, N -sinapoyl amide of memantine (3) emerges as the most potent antioxidant in all tests. Moreover, in vitro evaluation of anti-Alzheimer effects showed that the obtained memantine hybrids displayed neuroprotection in the moderate levels. Generally, they possess a little weaker activity as compared to the positive control memantine. Taken together, our findings reveal that the N -sinapoylamide of memantine (3) can be considered as a promising neuroprotective agent for Alzheimer's disease, acting as well as a potent radical scavenger. [Display omitted] [ABSTRACT FROM AUTHOR]