Sinteza i biološko vrednovanje novih derivata 2-fenil-benzimidazol-1-acetamida kao potencijalnih anthelmintika

The present study describes synthesis of a series of 2-phenyl benzimidazole-1-acetamide derivatives and their evaluation for anthelmintic activity using Indian adult earthworms, Pheretima posthuma. The structure of the title compounds was elucidated by elemental analysis and spectral data. The compounds 4-({[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]acetyl}amino) benzoic acid (3a), N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-benzyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3d), N-(4-hydroxyphenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3f), 2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl]-N-phenylacetamide (3h), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N\u27-phenylacetohydrazide (3k), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-(4-nitrophenyl) acetamide (3n) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenylacetamide (3q) were better to paralyze worms whereas N-ethyl-2-[2-(4-nitrophenyl)-1H-benzimidazol-1-yl] acetamide (3c), N-(4-nitrophenyl)-2-[2-(4-nitrophenyl)-1H-benzimidazol-1yl] acetamide (3e), 4-({[2-(4-chlorophenyl)-1H-benzimidazol-1-yl] acetyl} amino) benzoic acid (3j), 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-ethylacetamide (3l) and 2-[2-(4-chlorophenyl)-1H-benzimidazol-1-yl]-N-phenylacetamide (3q) were better to cause death of worms compared to the anthelmintic drug albendazole.U radu je opisana sinteza derivata 2-fenil-benzimidazol-1-acetamida i ispitivanje njihovog anthelmintičkog djelovanja na odrasle indijske gliste, Pheretima posthuma. Struktura sintetiziranih spojeva određena je elementarnom analizom i spektroskopskim metodama. Spojevi 4-({[2-(4-nitrofenil)-1H-benzimidazol-1-il]acetil}amino) benzojeva kiselina (3a), N-etil-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3c), N-benzil-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3d), N-(4-hidroksifenil)-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3f), 2-[2-(4-nitrofenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3h), 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N\u27-fenilacetohidrazid (3k), 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-(4-nitrofenil) acetamid (3n) i 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3q) jače paraliziraju gliste, a N-etil-2-[2-(4-nitrofenil)-1H-benzimidazol-1-il] acetamid (3c), 2-[2-(4-nitrofenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3h), 4-({[2-(4-klorfenil)-1H-benzimidazol-1-il]acetil}amino) benzojeva kiselina (3j), 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-etilacetamid (3l) i 2-[2-(4-klorfenil)-1H-benzimidazol-1-il]-N-fenilacetamid (3q) učinkovitije usmrćuju gliste nego anthelmintik albendazol

Photonic band gaps and defect states induced by excitations of Bose-Einstein condensates in optical lattices

We study the interaction of a Bose-Einstein condensate, which is confined in an optical lattice, with a largely detuned light field propagating through the condensate. If the condensate is in its ground state it acts as a periodic dielectric and gives rise to photonic band gaps at optical frequencies. The band structure of the combined system of condensed lattice-atoms and photons is studied by using the concept of polaritons. If elementary excitations of the condensate are present, they will produce defect states inside the photonic band gaps. The frequency of localized defect states is calculated using the Koster-Slater model.Comment: 10 pages, 1 figure, RevTe

Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib

Background: Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. Patients and methods: Patients were randomized to receive maintenance olaparib (300 mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4 weeks until disease progression, at discontinuation, and 30 days after last dose. Scores ranged from 0 to 100; a ≥10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. Results: Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P = 0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P = 0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P = 0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P = 0.32; HR 1.38; 95% CI 0.73, 2.63). Conclusions: HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. ClincalTrials.gov number: NCT02184195

Beneficial effects of training at the anaerobic threshold in addition to pharmacotherapy on weight loss, body composition, and exercise performance in women with obesity

Oguz Ozcelik,1 Yusuf Ozkan,2 Sermin Algul,1 Ramis Colak2,3 1Department of Physiology, 2Department of Endocrinology and Metabolic Disease, Faculty of Medicine, Firat University, Elazig, 3Department of Endocrinology and Metabolic Disease, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey Objective: The aim of this study was to determine and compare the effects of weight loss achieved through orlistat therapy alone or a combination of orlistat and an aerobic exercise training program on aerobic fitness and body composition in obese females.Methods: Twenty-eight obese patients were randomly assigned to receive 12-week treatment with hypocaloric diet&ndash;orlistat or diet&ndash;orlistat&ndash;exercise. Each participant performed an incremental ramp exercise test every 4 weeks to measure aerobic fitness. Fourteen participants performed continuous exercise (approximately 45 minutes per session) at a work rate corresponding to the anaerobic threshold three times per week.Results: A decrease in the fat mass to body weight ratio of 3.8% (P=0.006) was observed at the end of the 12 weeks in the orlistat group, while a decrease of 9.5% (P=0.001) was seen in the orlistat&ndash;exercise group. Maximal exercise capacity increased by 46.5% in the orlistat&ndash;exercise group and by 19.5% in the orlistat group.Conclusion: While orlistat therapy resulted in an improvement in body composition and aerobic fitness at the end of the 12-week period, its combination with exercise training provided improvements in the same parameters within the first 4 weeks of the study. These additional beneficial effects of combining aerobic exercise with orlistat therapy are important with regards to obesity-associated risk factors. Keywords: obesity, orlistat, body mass index, anaerobic threshold, aerobic fitnes

Synthesis and biological evaluation of 3,5-diaryl-pyrazole derivatives as potential antiprostate cancer agents

Prostate cancer is the most frequently diagnosed tumor in men and the second leading cause of cancer-associated mortality in most developed countries. 3,5-Diaryl substituted pyrazole derivatives (20–28) were prepared starting from related chalcones and biologically evaluated for in vitro growth inhibition activity against PC3 and DU145 human prostate cancer cell lines. Compounds 23, 26, and 28 were found to be more potent as compared to the other halogen-substituted derivatives. Especially, the 2-bromo-substituted pyrazole derivative (26) was found to be more potent against PC3 and DU145 cells. Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2) are known to be expressed in DU145 and PC3 cancer cells. The binding mode of the most selective compound 26 toward&nbsp;EGFR and VEGFR2 was investigated by employing docking simulations based on GLIDE standard precision (−5.912 and −6.949 kcal/mol, respectively)

Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents

The present study was carried out in the attempt to synthesize a new class of potential anticancer agents comprising eleven compounds (24–34) sharing the 3,5-diarylisoxazole as a core. The chemical structure of the new synthesized compounds was established by IR, 1H NMR, 13C NMR and elemental analysis. Their biological potential towards prostate cancer was evaluated by using cancer PC3 cells and non-tumorigenic PNT1a cells. Interestingly, compound 26 distinguished from others with a quite high selectivity value that is comparable to 5-FU. The binding mode of 26 towards Ribosomal protein S6 kinase beta-1 (S6K1) was investigated at a molecular level of detail by employing docking simulations based on GLIDE standard precision as well as MM-GBSA calculations

Personality Disorder: Association With Temperament and Psychopathy

Objective: The molecular genetic of personality disorders has been investigated in several studies; however, the association of antisocial behaviours with synaptosomal-associated protein 25 (SNAP25) gene polymorphisms has not. This association is of interest as SNAP25 gene polymorphism has been associated with attention-deficit hyperactivity disorder and personality.Methods: We compared the distribution of DdeI and MnlI polymorphisms in 91 young male offenders and in 38 sex-matched healthy control subjects. We also investigated the association of SNAP25 gene polymorphisms with severity of psychopathy and with temperament traits: novelty seeking, harm avoidance, and reward dependence.Results: The MnlI TIT and DdeI TIT genotypes were more frequently present in male subjects with antisocial personality disorder (APD) than in sex-matched healthy control subjects. The association was stronger when the frequency of both DdeI and MnlI TIT were taken into account. In the APD group, the genotype was not significantly associated with the Psychopathy Checklist Revised scores, measuring the severity of psychopathy. However, the APD subjects with the MnlI T/T genotype had higher novelty seeking scores; whereas, subjects with the DdeI T/T genotype had lower reward dependence scores. Again, the association between genotype and novelty seeking was stronger when both DdeI and MnlI genotypes were taken into account.Conclusion: DdeI and MnlI TIT genotypes may be a risk factor for antisocial behaviours. The association of the SNAP25 DdeI TIT and MnlI T/T genotypes with lower reward dependence and higher novelty seeking suggested that SNAP25 genotype might influence other personality disorders, as well

Turkish patients with treatment-resistant schizophrenia

Background: Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. it would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS.Methods: This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms.Results: Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks.Conclusion: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms. (C) 2007 Elsevier Inc. All rights reserved