Use of 5-[2-Ethoxyquinazolone-3-yl]-2-phthalimidomethylthiadiazole in the Synthesis of N- and C-Glycosides via Amadori Rearra

Synthesis of  novel   5-[2- aminoquinazolin-4-one-3-yl]-2- phthalimidomethylthiadiazole   2 from  5-[2-ethoxyquinazolin-4-one-3-yl]-2-phthalamidomethylthiadiazole.  The  behavior of  as a nitrogen nucleophile towards an ±-hydroxy-aldehyde,  such as glucose and formation of Amadori  rearrangement product (ARP) that has had occurred during the course of reaction was discussed. Keywords: N-Glycosides, ±-bromoglucose,  Amadori rearrangement, quinazolinon

Spectroscopic Investigations of β-Amyloid Interactions with Propofol and L-Arginine

Beta amyloid (Aβ) aggregation has been characterized to be responsible for several amyloid diseases. Fourier transform infrared (FTIR) spectroscopy, fluorescence, and atomic force microscopy (AFM) are used to investigate induced changes in the secondary structure of Aβ upon thermal denaturation and interaction with propofol and L-arginine. Spectral analysis has revealed an effective static quenching for the intrinsic fluorescence of Aβ by propofol and l-arginine with binding constants of 2.81 × 102 M−1 for Aβ-propofol and 0.37 × 102 M−1 for Aβ-L-arginine. Fourier self-deconvolution (FSD) technique has been used to evaluate the relative intensity changes in the spectra of the component bands in the amide I and amide II regions at different ligand’s concentration in the protein complex. The analysis showed a decrease in the intensities of the parallel beta bands of propofol and L-arginine interactions with Aβ, accompanied with an increase in the antiparallel bands for the Aβ-propofol interaction and a decrease for the Aβ-l-arginine interaction. The relative increase in peaks’ intensities at 1694 cm−1 and 1531 cm−1 for the propofol interaction is linked to the formation of oligomers in the protein.This work is supported by the German Research Foundation DFG grant No. DR228/24-2

Use of 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione in the Synthesis of Novel Quinazolinone Derivatives

The 2-{[5-(2-Amino-4-oxoquinazolin-3(4H)-yl)-1,3,4-thiadiazol-2-yl]methyl}-1H-isoindole-1,3(2H)-dione 1 was synthesized and allowed to react with each of  p-methoxybenzaldehyde,  p-methoxyacetophenone and chloroacetyl chloride to produce the Schiff bases 2 and 3 and 2-chloro-N-(3-{5-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-1,3,4-thiadiazol-2-yl}-4-oxo-3,4-dihydroquinazolin-2-yl)acetamide 6, respectively. The products 2 and 3 were reacted with phenyl isothiocyanate to afford 4 and 5. Derivative 6 was reacted with various nucleophiles, namely: thioglycolic acid, ethyl glycinate and 2-aminoethanol giving 7-9 respectively. In turn, the derivative 8 was reacted with α-bromoglucose tetraacetate affording product 8a whereas 9 was reacted with p-acetylaminobenzenesulfonyl chloride affording derivative 9a. Moreover, the reactions of the derivative 6 with potassium thiocyanate, potassium cyanate, malonitrile, ethyl cyanoacetate and ammonium acetate gave derivatives 10-15, respectively. All the synthesized derivatives were confirmed by the IR, mass, 1H-NMR and elemental analysis. Key words: Quinazolinyl thiazolidine, thioxodiazetidinyl quinazoline, piperazinyl quinazolinone, thiomorpholine and  triazinoquinazoline

Use of 2-Ethoxy(4H)-3,1-benzoxazin-4-one as a Precursor for Synthesis of Quinazoline and Quinazolinone Starting Materials

The interactions of 2-ethoxy(4H)-3,1-benzoxazin-4-one (1) with various nitrogen nucleophiles such as ammonium acetate,  hydrazine hydrate, ethanolamine, p-phenylenediamine, o-phenylenediamine, o-tolidine, dapsone, 2-aminophenol, 4-aminophenol, 4-aminobenzoic acid and 2-aminonicotinic acid have been discussed. The reactions of 2-thoxy-(3H)-quinazolin-4-one with ethyl chloroformate, phosphorus pentasulfide, chloroacetyl chloride and phosphorus oxychloride have also been investigated. Similar reactions of 2-ethoxy-4-chloroquinazoline with hydrazine hydrate and thiosemicarbazide have been introduced. Aminolysis of the 2-ethoxy group in some of the thiadiazoloquinazolinone derivatives has been attempted. The interactions of these aminolized derivatives and the 3-aminoquinazolinone with chloroacetyl chloride have been studied. All of the synthesized derivatives have been used in a wide range as starting materials for the synthesis of novel quinazoline and/or quinazolinones which have biological activity. The structures of all these products, obtained by heterocyclic ring opening and ring closure, were inferred by the IR, MS, 1H NMR spectral as well as elemental analyses. Keywords: Aminothiadiazole, Benzoxazin-4-one, N-nucleophile, quinazoline, quinazolin-4-one, thiosemicarbazide

Spectroscopic Characterization of the Interaction between Dopamine and Human Serum Albumin

The interactions of HSA with DA have received great attention nowadays due to its significant effect in the biomedical field and overall health. The main aim of this work is to examine the interaction between DA and HSA at physiological conditions. Upon addition of DA to HSA, the fluorescence emission was quenched with quenching constant Kq = 1.32 × 109 L∙mol−1∙s−1 and the binding constant of DA with HSA is found to be K = 4.4 × 102 mainly indicating dynamic quenching. The HSA conformation was altered upon binding of DA to HSA with an increase in α-helix and a decrease in β-sheets suggesting unfolding of HSA secondary structure due to weak intermolecular interaction with HSA. In view of the evidence presented, it is important to understand the details of the interactions of HSA with DA which will be crucial in the design of new DA-inspired drugs and help revealing vital details to better understand the HSA’s role as a transporter for many drugs.This work is supported by the German Research Foundation DFG Grant No. DR228/24-2

Serum vitamin D and IgE levels in infants and children under 2 years of age with recurrent chest wheeze

Background: Wheezing is a very common complaint on admission to the pediatric emergency department. There is an increasing awareness of the important role of vitamin D (VD) in the maintenance of the immune system, recurrent wheezing and respiratory health. Objective: The study aimed to estimate serum 25 hydroxy vitamin D (25OHD), IgE levels and blood eosinophilic count in infants and children under 2 years of age with recurrent wheeze. Methods: This case-control study was carried out on 85 infants (58 males and 27 females; as the patients’ group, ranging in age from 6-24 months, diagnosed to have recurrent wheeze (>3 attacks), recruited from the Pediatric Emergency Department in comparison to 85 age and gender matched healthy infants with no history of wheeze (as the control group). Blood samples were taken from both groups to determine serum 25OHD level, IgE level, and eosinophil count. Results: Serum 25OHD levels of patients were significantly lower than those of controls (p = 0.001), whereas serum IgE and eosinophil counts of patients were significantly higher than those of controls (p <0.0001 for both). Serum levels of 25OHD correlated negatively with the number of wheeze attacks and hospitalization. Conclusion: The study findings revealed lower serum 25OHD levels in infants with recurrent wheeze and provides additional evidence supporting the hypothesis that VD has a role in infant wheeze. VD supplementation might be practical and favorable for better control of recurrent infant wheeze.Keywords:Vitamin D, IgE, Infants, Wheeze

Biopiracy <i>versus </i>one-world medicine – from colonial relicts to global collaborative concepts

Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.Hypothesis: : The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine.Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients

Mapping inequalities in exclusive breastfeeding in low- and middle-income countries, 2000–2018

Abstract: Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for example, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17 : analysis for the Global Burden of Disease Study 2017

Background Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea. Methods We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates. Findings The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage. Interpretation By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health