SYNTHESIS, STRUCTURAL ELUCIDATION AND ANTIMICROBIAL EVALUATION OF 2-{4-(T-AMINO)-2-(BUT-2-YN-1-YL)}-1, 3 BENZOTHIAZOLE DERIVATIVES

Objective: A new series of 2-{4-(t-amino)-2-(but-2-yn-1-yl)}-1,3-benzothiazole derivatives, 2-[4-(pyrrolidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ2), 2-[4-(2-methylpiperidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ3), 2-[4-(piperidin-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ4), 2-[4-(azepan-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ5), 2-[4-(4-methylpiperazin-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ6), 2-[4-(2, 6-dimethylpiperidin-1-yl) but-2-yn-1-yl]-1, 3-benzothiazole (BZ7) were synthesized and screened in vitro as potential antimicrobial agents.Methods: In-vitro antimicrobial activity evaluation was done, by agar diffusion method and broth dilution test against Staphylococcus aureus ATCC 6538p, Candida albicans ATCC 10231, Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, and Bacillus subtilis ATCC 6633. Minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) were determined. The results of antimicrobial testing were compared to two positive control drugs ciprofloxacin (5 µg/ml) and fluconazole (500µg/ml).Results: Compound 2-[4-(azepan-1-yl) but-2-yn-1-yl]-1,3-benzothiazole (BZ5) showed the highest antibacterial activity against S. aureus with MIC value of 15.62 µg/ml while; Compound 2-[4-(2,6-dimethylpiperidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ7) exhibited the highest antibacterial activity against P. aeruginosa with MIC value of 31.25 µg/ml. Compounds 2-[4-(pyrrolidin-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ2) and 2-[4-(azepan-1-yl)but-2-yn-1-yl]-1,3-benzothiazole (BZ5) showed the highest antifungal activity against C. albicans with MIC value of 15.62 µg/ml (for both).Conclusion: The results obtained showed variation in the antibacterial and antifungal activity based on the structure of the cyclic amines in these amino acetylenic benzothiazole derivatives. Keywords: Benzothiazole, Aminoacetylenic, Antibacterial, Antifungal, Mannich reactio

Physico-Chemical and Microbiological Studies on Jordanian Honey and Propolis as Potential Self-Preserving Pharmaceutical Systems

The aim of this project was to study the physico-chemical and antimicrobial properties of Jordanian honey and propolis in order to determine their potential as pharmaceutical preservation systems. This study undertook a physico-chemical analysis of several Jordanian honeys and one propolis type, in order to evaluate several physico-chemical properties including, pH and free acidity, moisture content, ash content and HydroxyMethylFurfural content in three honey samples, and total flavonoid content in the propolis sample. The antimicrobial activity of honey and propolis samples was then evaluated by determining the minimum inhibitory concentration (MIC) against Staphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Subsequently, Honey 1 (H1) was selected for further study and combined with propolis to test their potential synergistic activity. Finally, a preservative effectiveness test was conducted in order to assess the possibility of using honey and propolis as natural preservatives in aqueous dosage forms, such as syrups. The results of this study showed that all the tested honey samples and propolis possessed significant antimicrobial activity against the standard test microorganisms, and that honey with propolis exhibited synergistic activity that enhanced their antimicrobial activity and resulted in up to 90% reduction in their MIC values. This study also confirmed that honey and propolis could be used as a natural preservative system for pharmaceutical formulae. Our results reveal the possibility of using honey-propolis mixtures as natural preservatives in oral aqueous pharmaceutical dosage forms and other local application products

CHEMICAL CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF JORDANIAN PROPOLIS AND NIGELLA SATIVA SEED OIL AGAINST CLINICALLY ISOLATED MICROORGANISMS

Objective: Increasing use of medicinal plants in the treatment of infectious diseases are due to the development of multi-antibiotics resistant microorganisms, and had alerted our interest in the examination of some natural products. This study was carried out to investigate the antimicrobial activity of Jordanian propolis, black seed oil (Nigella sativa) extract, alone or in combination against clinically isolated microorganisms (bacteria and fungi).Methods: Jordanian propolis samples were collected. Aqueous and alcoholic extractions were done; black seed oil was extracted from Nigella sativa seeds. Seven clinical isolated microorganisms namely: Micrococcus luteus, Bacillus pumilus, Bordetella bronchisptica, Enterococcus fecalis, Bacillus subtilis, and Staphylococcus aureus, and one yeast strain namely Candida albicans were used. The antimicrobial activity was investigated by agar diffusion technique and microplate dilution to determine the MIC.Results: The results indicated that the alcoholic propolis extract showed higher antimicrobial activity than the aqueous propolis extract. The antimicrobial activity of black seed oil was significantly higher than that of the propolis. Mixing propolis with black seed oil showed synergism effects against some microorganisms as Enterococcus fecalis (24±1.1), Bordetella bronchisptica (20±0.9) and Candida albicans (40±2.3), and additive with others as Bacillus subtilis (28±1.8).Conclusion: Black seed oil and propolis might be used as a potential source of safe and effective natural antimicrobial in pharmaceutical and food industries

Antimicrobial tolerance changes in biocide-passaged biofilm cultures of Pseudomonas aeruginosa PAO1

The aim of this study was to develop a novel process for the passaging of biofilms of Pseudomonas aeruginosa towards tolerance to a group of selected antimicrobial agents (biocides). The combination of both a traditional passage approach coupled with a suitable biofilm model, for the production of large numbers of adherent cells, yielded evidence of a development of phenotypic tolerance in Ps. aeruginosa towards selected biocides (zinc pyrithione (ZnPT), sodium pyrithione (NaPT), Cetrimide & Benzisothiazolone (BIT)). The results indicate a step-wise increase in minimal inhibitory concentration (MIC) over a series of ten consecutive passages in the presence of increasing concentrations of biocide. Scanning electron microscopy revealed a complex internal structure to the biofilms grown using this model. Results indicate that it is possible to passage cultures of Ps. aeruginosa towards phenotypic tolerance to selected antimicrobial agents. Results also indicate that such tolerance is partially reversible and that some residual tolerance remains in the absence of biocide. Thus, indicating that the tolerance is partially due to phenotypic changes within biofilm cells. This study describes a novel technique for the induction of phenotypic tolerance towards antimicrobial agents in biofilm situations. The model used here may be adapted to other areas of biofilm work, where clonal selection of phenotypic traits may be desirable

A review of the antimicrobial activity of thermodynamically stable microemulsions

Microemulsions are thermodynamically stable, transparent, isotropic mixtures of oil, water and surfactant (and sometimes a co-surfactant), which have shown potential for widespread application in disinfection and self-preservation. This is thought to be due to an innate antimicrobial effect. It is suggested that the antimicrobial nature of microemulsions is the result of a combination of their inherent kinetic energy and their containing surfactants, which are known to aid the disruption of bacterial membranes. This review examines the contemporary evidence in support of this theory.</p

DESIGN, SYNTHESIS AND BIOLOGICAL SCREENING OF AMINOACETYLENIC TETRAHYDROPHTHALIMIDE ANALOGUES AS NOVEL CYCLOOXYGENASE (COX) INHIBITORS

Objective: To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs.Methods: Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione. The alkylated tetrahydro phthalimide was subjected to Mannich reaction afforded the desired amino acetylenic tetra phthalimide derivatives (AZ 1-6). The elemental analysis was indicated by the EuroEA elemental analyzer and biological characterization was via IR, 1H-NMR, [13]C-NMR, DSC was determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d6 as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes.Results: The IR, 1H-NMR, 13C-NMR, DSC and elemental analysis were consistent with the assigned structures. The designers of the compounds as COXs inhibitor activity were based on the nationalisation of the important criteria that provide effective inhibitory binding with COXs–receptor. The results indicated that the synthesised compounds (AZ1-6) showed a close similarity in the binding affinity to both COXs and may be more specific to COX-1. AZ-5 showed the highest % of inhibition for COX-1 even better than aspirin. Which may suggest that the aryl group is required for COX-2 inhibition.Conclusion: For the first time, we indicate the requirement of aromaticity in COX-2 structural inhibitory activity.Â

Water-in-oil microemulsions exhibit antimicrobial activity

Objectives: Previous research from this group has identified significant antimicrobial activity associated with oil-in-water (O/W) microemulsions. This activity has been exhibited against both bacteria and fungi (including yeasts) and bacterial biofilms and is dependent upon the position of the microemulsion within its stability zone. This novel work aims to identify antimicrobial activity of water-in-oil (W/O) microemulsions. Materials &amp; Methods: A simple, thermodynamically stable water-in-oil microemulsion was tested for its time-related antimicrobial activity against a selected panel of test microorganisms (i.e.: Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, Candida albicans ATCC 10231 and Staphylococcus aureus ATCC 6538P) and its effectiveness as a self-preserving system against a similar panel (Pseudomonas aeruginosa ATCC 9027, Candida albicans ATCC 10231, Staphylococcus aureus ATCC 6538P and Aspergillus niger ATCC 16404). Results: The microemulsion exhibited significant antimicrobial activity against all the selected microorganisms. Decreases in the viability of cultures (P. aeruginosa, C. albicans, E. coli and S. aureus) were observed over a short period of time after exposure to a known concentration of the first microemulsion. The results for the four samplings in the preservative effectiveness test according to the European Pharmacopeia requires a significant reduction in bacterial count, and this requirement was achieved in all samplings. Conclusions: Thermodynamically stable water-in-oil microemulsions are antimicrobially active, self-preserving systems, as are their oil-in-water counterparts

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations