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2021
Elamragy, A., A. Hussein, A. Kaddah, and M. Meshaal, "Neutrophil: Lymphocyte Ratio Predicts Coronary Artery Disease Severity in Non-ST Elevation Myocardial Infarction Using Syntax Score", Benha Medical Journal, pp. 0 - 0, 2021/01//. AbstractWebsite
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Ibrahim, H., A. M. Hamdy, H. A. Merey, and A. S. Saad, "Simultaneous Determination of Paracetamol, Propyphenazone and Caffeine in Presence of Paracetamol Impurities Using Dual-Mode Gradient HPLC and TLC Densitometry Methods", Journal of Chromatographic Science, vol. 59, issue 2, pp. 140 - 147, 2021/01//. AbstractWebsite

Two chromatographic methods were validated for the determination of the widely prescribed analgesic and antipyretic drug combination of paracetamol (PC) (recently integrated into the supportive treatment of COVID-19), propyphenazone (PZ) and caffeine (CF) in the presence of two PC impurities, namely 4-aminophenol and 4-nitrophenol. A “dual-mode” gradient high-performance liquid chromatography method was developed, where the separation was achieved via “dual-mode” gradient by changing both the ternary mobile phase composition (acetonitrile: methanol: water) and the flow rate. This enables a good resolution within a relatively shorter analysis time. The analysis was realized using Zorbax Eclipse XDB column C18, 5 μm (250 × 4.6 mm) and the UV detector was set at 220 nm. The other method is a thin-layer chromatography densitometry method, where the separation was achieved using a mobile phase composed of chloroform: toluene: ethyl acetate: methanol: acetic acid (6: 6: 1: 2: 0.1, by volume). Densitometric detection was performed at 220 nm on silica gel 60 F254 plates. The developed methods were fully validated as per the ICH guidelines and proved to be accurate, robust, specific and suitable for application as purity indicating methods for routine analysis of PC in pure form or in pharmaceuticals with PZ and CF in quality control laboratories.

EL-SAYED, B. A. S. M. A., M. O. H. A. M. E. D. ESSA, and M. El-Beltagy, "MODELING AND CONTROL OF AIRCRAFT PILOT STICK BASED ON ANFIS, CUCKOO SEARCH ALGORITHM AND SYSTEM IDENTIFICATION", 1st. Inter. E-Conf. in Math. Sciences and Fractional Calculus(ICMSFC Feb 2021)., Egypt, 2021//2. 7vol.123.no_.7pp.1-10.pdf
Elmehrath, A. O., A. M. Afifi, M. J. Al-Husseini, A. M. Saad, N. Wilson, K. S. Shohdy, P. Pilie, M. B. Sonbol, and O. Alhalabi, "Analysis of Causes of Death among Patients with Metastatic Prostate Cancer in the United States, 2000-2016", JAMA Network Open, vol. 4, issue 8, pp. e2119568 - e2119568, 2021///. Abstract
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Abd Elfadeel, S. M., H. Amein, M. M. El-Bakry, and M. A. Hassan, "Assessment of a multiple port storage tank in a CPC-driven solar process heat system", Renewable Energy, vol. 180: Elsevier Ltd, pp. 860 - 873, 2021///. AbstractWebsite

Sensible thermal energy storage is the most common solution for small-to-medium solar process heat systems. Hence, it is vital to enhance the thermal stratification and energy utilization of stratified tanks. In this study, four process heat systems are dynamically simulated: 1) S0 with a single outlet port to the load, 2) S1 with a single port and a thermostatic mixing valve, 3) M0 with multiple ports, and 4) M1 with multiple ports and a mixing valve. Two novel models are proposed for the compound parabolic collectors and the stratified tanks. System M1, with annual system efficiency of 47.3% and solar fraction of 0.57, was found to be the best-performing one, followed by S1, M0, and S0. System M1 also reduced the annual energy consumption of the backup heater in S0 by 16.45%. The thermostatic mixing valve reduced the thermocline thickness. The incorporation of both mixing valve and multiple ports delayed the startup of the heater, reduced the system's thermal losses, and slightly improved the collectors' efficiencies. The proposed tank model can be a viable tool for solar energy designers to optimize the number and relative positions of the inlet and outlet ports for maximized system efficiency and solar coverage.

Abdelmoniem, A. M., I. A. Abdelhamid, and H. Butenschön, "Bidirectional Synthesis, Photophysical and Electrochemical Characterization of Polycyclic Quinones Using Benzocyclobutenes and Benzodicyclobutenes as Precursors", European Journal of Organic Chemistry, vol. 2021, issue 46, pp. 6319 - 6333, 2021///. Abstract

Quinones have widespread applications in view of their interesting chemical and photophysical features. On the other hand, benzocyclobutenes (BCBs) are generally masked reactive dienes suitable for the [4+2] cycloaddition reactions. Here, benzocyclobutenes and benzodicyclobutenes (BDCBs) were prepared and further reacted with benzoquinone and naphthoquinone in order to obtain some new polycyclic quinones with highly extended π systems, namely, 6-bromo-5,8-dimethoxyanthracene-1,4-dione, 2,9-dibromo-1,4,8,11-tetramethoxypentacene-6,13-dione, 9-bromo-7,10-dimethoxytetracene-5,12-dione, 3,10-dimethoxycyclobuta[b]anthracene-1,5,8(2H)-trione, 6,10,17,21-tetramethoxynonacene-1,4,8,12,15,19-hexaone, and 3,12-dimethoxycyclobuta[b]tetracene-1,5,10(2H)-trione. In addition to their spectroscopic characterization the new compounds are investigated by UV and fluorescence spectroscopy, cyclic voltammetry, and DFT calculations.

Wahba, M. E., D. El Wasseef, A. S. Saad, and M. E. Draz, "Calixarene based portable sensor for the direct assay of indiscriminate ephedrine content of weight loss herbal preparations", RSC Advances, vol. 11, issue 21: Royal Society of Chemistry, pp. 12833 - 12844, 2021///. AbstractWebsite

A novel potentiometric sensor was developed and optimized for the quantitative analysis of ephedrine in non-prescribed herbal supplements used as adjunctive therapy for weight loss. An initial optimization study aimed to reach the optimum membrane composition, sensor assembly, and experimental conditions. The study evaluated the effect of several factors on the sensor performance including different ion-exchangers, plasticizers, ionophores, membrane thicknesses, soaking solution concentrations, soaking time intervals, and pH. The optimized polyvinyl chloride membrane included tungstophosphoric acid hydrate as a cation exchanger, tricresyl phosphate as a plasticizer, and calix[8]arene as an ionophore to enhance the sensitivity and selectivity of the developed sensor. The polyvinyl chloride membrane was drop-casted over a polyaniline modified glassy carbon electrode surface to form a solid-state sensor. The proposed membrane succeeded to quantify ephedrine over a linear range of 6 × 10−6to 1 × 10−2M with a LOD of 3.60 × 10−6M, acceptable selectivity, and fast response time. The IUPAC characterization of sensor response and International Conference on Harmonization validation parameters were calculated. The method successfully determined ephedrine concentration in spiked herbal mixtures and determined labeled and undeclared ephedrine content of weight loss herbal preparations.

Edrees, F. H., A. S. Saad, M. T. Alsaadi, N. H. Amin, and N. S. Abdelwahab, "Experimentally designed chromatographic method for the simultaneous analysis of dimenhydrinate, cinnarizine and their toxic impurities", RSC Advances, vol. 11, issue 3, pp. 1450 - 1460, 2021///. AbstractWebsite

Experimentally designed HPLC method for simultaneous analysis of dimenhydrinate, cinnarizine and their toxic impurities.

Abdelmoniem, A. M., M. G. M. Abdelrahman, S. A. S. Ghozlan, A. H. M. Elwahy, and I. A. Abdelhamid, "Hantzsch reaction with bis-indole-2,3-diones: Synthesis of novel bis-spirocyclic oxindole incorporating acridine, dipyrazolo[3,4-b:4',3'-e]pyridine and pyrido[2,3-d:6,5-d']dipyrimidine", Synthetic Communications, vol. 51, issue 12: Taylor & Francis, pp. 1814 - 1824, 2021///. Abstract

One-pot three-component cyclo-condensation reaction of bis(indole-2,3-diones) with dimedone, 3-methyl-1H-pyrazol-5(4H)-one, or 6-aminouracil in boiling acetic acid afforded bis-spirocyclic oxindoles linked to acridine, dipyrazolo[3,4-b:4',3'-e]pyridine, and pyrido[2,3-d:6,5-d']dipyrimidine, respectively.

Hassan, M. A., B. M. Akoush, M. Abubakr, P. E. Campana, and A. Khalil, "High-resolution estimates of diffuse fraction based on dynamic definitions of sky conditions", Renewable Energy, vol. 169: Elsevier Ltd, pp. 641 - 659, 2021///. AbstractWebsite

Accurate monitoring and operation of solar power systems require high-resolution solar radiation measurements and precise separation models. This study aims to improve the accuracy of classic diffuse fraction-clearness index piecewise separation models by applying data-driven classifications of sky conditions. This is achieved through a novel outlier-insensitive clustering algorithm and shape prescriptive modeling, applied to 1-, 10-, 30-, and 60-min ground measurements from 4 different locations in the MENA region. This study shows that classifications of sky conditions are not uniform among the selected locations even though all stations fall in the arid desert climate category. This highlights the importance of extracting the sky conditions from measurements rather than using available classifications in the literature. The selection of the number of clusters has to undergo optimization. The number of clusters is also a function of the time resolution. One of the selected locations shows four optimal clusters for 1-min data and six clusters for 60-min data. All developed piecewise separation models show high accuracy and stability with the mean bias errors approaching zero values and the mean absolute errors ranging between 8.7 and 11.8%. The models also outperform existing ones and have good generalization capabilities under the same climate classification.

el-Aziz, A. A., M. A. El-Desouky, A. Shafei, M. Elnakib, and A. M. Abdelmoniem, "Influence of pentoxifylline on gene expression of PAG1/ miR-1206/ SNHG14 in ischemic heart disease", Biochemistry and Biophysics Reports, vol. 25: Elsevier, pp. 100911 - 100911, 2021///. Abstract

The regulation by immune checkpoint is able to prevent excessive tissue damage caused by ischemia reperfusion (I/R); therefore, the study aims to investigate the behavior of phosphoprotein associated with glycosphingolipid-enriched microdomains 1 (PAG1) mRNA, miR-1206 and small nucleolar RNA host gene 14 (SNHG14) during I/R and intake of pentoxifylline (PTX) as a protective drug. The relative expression level of PAG1/miR-1206/SNHG14 was determined by qRT-PCR. Cardiac tissue levels of cytotoxic T-lymphocyte associated antigen 4 (CTLA4) and PAG1 protein expression were determined by ELISA technique. The regulatory T cells achieved by the flow cytometry. The results found that the relative expression of SNHG14 was significantly upregulated in I/R, but suppressed in PTX treated groups with enhancement of the relative expression level of miR-1206. The gene and protein expression of PAG1 were downregulated with effective doses of PTX. The results showed that (30 and 40 mg/kg bwt) PTX dose suppressed the CTLA4 development significantly. The mean of the regulatory T cell in PTX protective groups is significantly reduced at (p < 0.001) in a comparison with I/R group. Spearman's correlation analysis revealed a significant negative correlation between SNHG14 and miR-1206, but a significant positive correlation between SNHG14 and PAG1 in I/R heart tissue. The results indicated that miR-1206 and SNHG14 can be used as biomarkers with perfect sensitivity and specificity. Using PTX reduced cardiac tissue damage. SNHG14 and miR-1206 can be used as a diagnostic tool in I/R.

Amein, H., M. A. Kassem, S. Ali, and M. A. Hassan, "Integration of transparent insulation shells in linear solar receivers for enhanced energy and exergy performances", Renewable Energy, vol. 171: Elsevier Ltd, pp. 344 - 359, 2021///. AbstractWebsite

This study investigates the performance enhancement of parabolic trough concentrators (PTCs) with transparent insulation material shell (TIMS) of different diameters and thicknesses integrated into evacuated and non-evacuated heat collection elements (HCEs). The results show that non-evacuated TIMS-HCEs have higher energy and exergy efficiencies by up to 62.4 and 63.2%, compared to conventional evacuated HCEs, and by up to 109.2 and 110.9%, compared to conventional non-evacuated HCEs. At high flow rates and low fluid temperatures, the energetic performance of a conventional evacuated HCE is only 6.3% higher than that of the modified non-evacuated one. The modified design also enhances the circumferential temperature uniformity and shows a marginal drop in efficiency when the vacuum is lost. By simulating the PTC performance during four typical days, and without vacuum, the proposed design increased the daily useful heat gain by up to 1.36 and 5.64 kWh, compared to conventional evacuated and non-evacuated HCEs, respectively. Hence, it is proposed as a low-tech alternative to HCE evacuation and as a method of boosting the performance of PTCs operating at low flow rates and high temperatures.

El-Bakry, M. M., M. A. Kassem, and M. A. Hassan, "Passive performance enhancement of parabolic trough solar concentrators using internal radiation heat shields", Renewable Energy, vol. 165, pp. 52 - 66, 2021///. Abstract

Boosting the optical and thermal efficiencies of parabolic trough concentrators is gaining renewal global interest for improving the overall concentrating solar power plant efficiency and reducing the specific costs of power generation. Using internal radiation heat shields in the annular space of the heat collection element is an attractive passive solution that is not well-addressed in the literature. This study is a first attempt to analyze and map both energetic and exergetic performances of parabolic trough concentrators in terms of the configuration of the radiation heat shield and the operating conditions of the concentrator. A 3D model based on Monte-Carlo ray tracing and computational fluid dynamics is developed, validated, and used to examine 420 combinations of design and operating parameters. The proposed design outperformed the conventional one in the whole spectrum of operating conditions, except for a narrow range of low operating temperatures and high flow rates. Floating radiation heat shields with small diameters and large shading angles enhanced the temperature uniformity of heat collection element and showed the highest enhancement ratios of both energy and exergy efficiencies, which were up to 15.4 and 14.4%, respectively. A radiation heat shield with a diameter of 75 mm and a shading angle of 150° was found the best performing configuration for most operating conditions. Increasing the shield's emissivity (0.06) to that of the absorber tube (0.14) reduced the energy and exergy efficiencies by up to 33.75 and 29.06%, respectively. The effectiveness of the modified design was more pronounced at lower solar irradiance levels. The enhancements of energy and exergy efficiency decreased by 85.76 and 86.40% as the irradiance increased from 200 to 1000 W/m2. However, the modified design was still more efficient at all considered values of emissivity and solar irradiance.

Kaood, A., M. Abubakr, O. Al-Oran, and M. A. Hassan, "Performance analysis and particle swarm optimization of molten salt-based nanofluids in parabolic trough concentrators", Renewable Energy, vol. 177: Elsevier Ltd, pp. 1045 - 1062, 2021///. AbstractWebsite

Molten salts are typically used as energy storage media in concentrating solar power systems for their lower costs and environmental impact. This study aims to map and optimize the performance of parabolic trough concentrators (PTCs) working with molten salt-based nanofluids (MSNFs) as heat transfer media at high temperatures. The thermal, hydraulic, energetic, and exergetic performances were analyzed and optimized using a unique framework of Monte Carlo optical simulations, computational fluid dynamics, data-drive support vector regression, particle swarm optimization, and decision-making techniques. Three molten salts (Solar Salt, Hitec, and Hitec XL) and three nanoparticle types (Al2O3, CuO, and SiO2) were investigated in a broad range of volumetric concentrations (0.0–4.0%), operating Reynolds numbers (4 × 103 to 40 × 103), and temperatures (535–805 K). The results showed a maximum energy efficiency of 69.1%, achieved when using SiO2-Hitec nanofluid (1.0%) at a Reynolds number of 40 × 104 and temperature of 535 K. The maximum achieved exergy efficiency was 70.48%, obtained using pure Hitec at a Reynolds number of 40 × 104 and temperature of 535 K. The maximum possible enhancements in energy and exergy efficiencies in the covered range are 17.0 and 42.0%, respectively. The optimal combination of energy and exergy efficiencies are ∼73.1 and 69.0%, obtained using CuO-Hitec nanofluid at temperature, Reynolds number, and concentration of 535 K, 39912.98, and 0.019%, respectively. The optimum combination of percentage enhancements in energy and exergy efficiencies are 0.465 and 7.182%, respectively, which corresponds to CuO-Hitec nanofluid operating at 805 K, 32025.4, and 0.092%, respectively.

Abubakr, M., M. A. Hassan, G. M. Krolczyk, N. Khanna, and H. Hegab, "Sensors selection for tool failure detection during machining processes: A simple accurate classification model", CIRP Journal of Manufacturing Science and Technology, vol. 32: CIRP, pp. 108 - 119, 2021///. AbstractWebsite

Tool failure detection is a crucial task for continuous safe machining operations. In this study, a novel approach is proposed to develop an accurate and simple tool condition classification model (TCCM) for early failure detection during machining processes. Signals from current, vibration, and acoustic emission sensors were preprocessed and used for feature extraction in both time and frequency domains, leading to a total of 152 features. Next, a feature reduction was carried out based on relative importance, computed using a fully-grown random forest, which reduced the number of features to 15. To find out the best combination of relevant signal features, a total of 32,767 optimized support vector classifiers were developed. The comparison between different candidate models was based on both accuracy and complexity. The results showed that a classification accuracy up to 0.911 is attainable for a process-independent classification model using only current sensors. Besides, developing an ensemble of material-dependent models showed a good potential for improvement, recording a classification accuracy up to 0.958 while using features extracted only from the current sensors. The novelty in the present study is in its focus on developing a single sensor-based high-accuracy TCCM. This opens the door for wider utilization of such technology, especially that all existing studies focused on increasing the accuracy using multi-sensor TCCMs, which increases the cost of this technology and makes it inaccessible, especially for small and medium enterprises.

Hassan, M. A., N. Bailek, K. Bouchouicha, and S. C. Nwokolo, "Ultra-short-term exogenous forecasting of photovoltaic power production using genetically optimized non-linear auto-regressive recurrent neural networks", Renewable Energy, vol. 171: Elsevier Ltd, pp. 191 - 209, 2021///. AbstractWebsite

Accurate and credible ultra-short-term photovoltaic (PV) power production prediction is very important in short-term resource planning, electric power dispatching, and operational security for the solar power system. This study proposes a novel approach of using genetically optimized non-linear auto-regressive recurrent neural networks (NARX) for ultra-short-term forecasting of PV power output. Hence, the high prediction accuracy of static multi-layered perceptron neural networks can be extended to dynamic (time-series) models with a more stable learning process. Exogenous models with different commonly available meteorological input parameters are developed and tested at five different locations in Algeria and Australia, as case studies of the arid desert climate. The prediction capabilities of the models are quantified as functions of the forecasting horizon (5, 15, 30, and 60 min) and the number of meteorological inputs using various statistical measures. It was found that the proposed models offer very good estimates of output power, with relative root mean square errors ranging between ∼10 and ∼20% and coefficients of determination higher than 91%, while improving the accuracy of corresponding endogenous models by up to 22.3% by only considering the day number and local time as external variables. Unlike the persistent model, the proposed NARX-GA models perform better as the forecasting horizon narrows down, with improvements of up to 58.4%.

Alsirafy, S. A., R. Nagy, A. D. Hassan, R. Fawzy, A. A. M. Abdelhafeez, M. O. Husein, M. A. Almashiakhi, S. H. Alabdullateef, S. A. Alghamdi, and A. M. Elyamany, "Caregiver burden among family caregivers of incurable cancer patients in two eastern Mediterranean countries.", BMC palliative care, vol. 20, issue 1, pp. 163, 2021 Oct 18. Abstract

BACKGROUND: Although family caregivers (FCs) play an important role in the care provided to incurable cancer patients in our region, little is known about the burden they experience. This study was conducted to determine the prevalence of caregiver burden (CB) among FCs of incurable cancer patients in two Eastern Mediterranean countries and to identify factors that may be associated with significant CB.

METHODS: The study included 218 FCs, 165 from Egypt and 53 from Saudi Arabia. The 22-item Zarit Burden Interview (ZBI-22) was used to assess caregiver burden CB. Significant CB was defined as a ZBI-22 score ≥ 21. The assistance with basic ADLs was classified into 3 levels according to FCs' assistance with early/middle/late-loss basic ADLs. The relationship between CB and the assistance with ADLs and other factors was studied.

RESULTS: The mean (SD) ZBI-22 score among FCs was 23.4 (9.3) and the majority (128/218, 59%) had significant CB. Eighty-nine percent of FCs assisted with at least one basic ADL. Assistance with late-loss basic ADLs, best supportive care treatment plan and poorer performance status were associated with higher CB (p < 0.0001, =0.018 and = 0.005). However, in logistic regression analysis, only assistance with late-loss ADLs was independently associated with significant CB (OR = 3.4 [95%CI:1.2-9.7], p = 0.024).

CONCLUSION: A substantial proportion of FCs of incurable cancer patients in our region experience significant CB. Family caregivers assisting with late-loss basic ADLs are at risk of significant CB and should be routinely screened for CB.

ElAdl, N. M., H. M. Sholkamy, and E. S. Aala'a, 1-Year Post-loading of Short and Ultrashort Implants in Posterior Mandibular and Maxillary Regions, , vol. 9, issue D, pp. 264 - 269, 2021. Abstract
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Salama, E. S., R. A. El-Khoribi, M. E. Shoman, and M. W. A. Shalaby, A 3D-convolutional neural network framework with ensemble learning techniques for multi-modal emotion recognition, , vol. 22, issue 2: Elsevier, pp. 167 - 176, 2021. Abstract
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Arya, A., R. Chahal, R. Rao, M. H. Rahman, D. Kaushik, M. F. Akhtar, A. Saleem, S. M. A. Khalifa, H. R. El-Seedi, M. Kamel, et al., "Acetylcholinesterase inhibitory potential of various sesquiterpene analogues for alzheimer’s disease therapy", Biomolecules, vol. 11, issue 3, pp. 1 - 30, 2021. AbstractWebsite
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AbdElgawad, H., G. Zinta, W. Abuelsoud, Y. M. Hassan, D. H. M. Alkhalifah, W. N. Hozzein, R. Zrieq, G. T. S. Beemster, and S. Schoenaers, An actinomycete strain of Nocardiopsis lucentensis reduces arsenic toxicity in barley and maize, , vol. 417, pp. 126055, 2021. AbstractWebsite

Accumulation of arsenic in plant tissues poses a substantial threat to global crop yields. The use of plant growth-promoting bacterial strains to mitigate heavy metal toxicity has been illustrated before. However, its potential to reduce plant arsenic uptake and toxicity has not been investigated to date. Here, we describe the identification and characterization of a Nocardiopsis lucentensis strain isolated from heavy metal contaminated soil. Inoculation with this bioactive actinomycete strain decreased arsenic root and shoot bioaccumulation in both C3 and C4 crop species namely barley and maize. Upon arsenate treatment, N. lucentensis S5 stimulated root citric acid production and the plant’s innate detoxification capacity in a species-specific manner. In addition, this specific strain promoted biomass gain, despite substantial tissue arsenic levels. Detoxification (metallothionein, phytochelatin, glutathione-S-transferase levels) was upregulated in arsenate-exposed shoot and roots, and this response was further enhanced upon S5 supplementation, particularly in barley and maize roots. Compared to barley, maize plants were more tolerant to arsenate-induced oxidative stress (less H2O2 and lipid peroxidation levels). However, barley plants invested more in antioxidative capacity induction (ascorbate-glutathione turnover) to mitigate arsenic oxidative stress, which was strongly enhanced by S5. We quantify and mechanistically discuss the physiological and biochemical basis of N. lucentensis-mediated plant biomass recovery on arsenate polluted soils. Our findings substantiate the potential applicability of a bactoremediation strategy to mitigate arsenic-induced yield loss in crops.

Elbadry, Y. T., A. G. Guaily, M. A. Boraey, and M. M. Abdelrahman, Active Morphing Control of Airfoil At Low Reynolds Number Using Level-Set Method, : IEEE, pp. 265 - 268, 2021. Abstract
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Aziz, A. S., R. A. El-Khoribi, and S. A. Taie, Adaptive E-learning recommendation model based on the knowledge level and learning style, , vol. 99, issue 22, pp. 5241 - 5256, 2021. Abstract
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Sonousi, A., J. C. K. Quirke, P. Waduge, T. Janusic, M. Gysin, K. Haldimann, S. Xu, S. N. Hobbie, S. - H. Sha, J. Schacht, et al., "An Advanced Apralog with Increased in vitro and in vivo Activity toward Gram-negative Pathogens and Reduced ex vivo Cochleotoxicity", ChemMedChem, vol. 16, issue 2: John Wiley & Sons, Ltd, pp. 335 - 339, 2021. AbstractWebsite

Abstract We describe the convergent synthesis of a 5-O-?-D-ribofuranosyl-based apramycin derivative (apralog) that displays significantly improved antibacterial activity over the parent apramycin against wild-type ESKAPE pathogens. In addition, the new apralog retains excellent antibacterial activity in the presence of the only aminoglycoside modifying enzyme (AAC(3)-IV) acting on the parent, without incurring susceptibility to the APH(3?) mechanism that disables other 5-O-?-D-ribofuranosyl 2-deoxystreptamine type aminoglycosides by phosphorylation at the ribose 5-position. Consistent with this antibacterial activity, the new apralog has excellent 30?nM activity (IC50) for the inhibition of protein synthesis by the bacterial ribosome in a cell-free translation assay, while retaining the excellent across-the-board selectivity of the parent for inhibition of bacterial over eukaryotic ribosomes. Overall, these characteristics translate into excellent in?vivo efficacy against E. coli in a mouse thigh infection model and reduced ototoxicity vis à vis the parent in mouse cochlear explants.

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