Search results for: compound distributions

Authors: Farah Naja, Nahla Hwalla, Leila Itani, Shirine Baalbaki, Abla Sibai, Lara Nasreddine

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Purpose: To propose an index for assessing adherence to a Middle-Eastern version of the Mediterranean diet as represented by the traditional Lebanese Mediterranean diet (LMD), to evaluate the association between the LMD and selected European Mediterranean diets (EMD); to examine socio-demographic and lifestyle correlates of adherence to Mediterranean diet (MD) among Lebanese adults. Methods: Using nationally representative dietary intake data of Lebanese adults, an index to measure adherence to the LMD was derived. The choice of food groups used for calculating the LMD score was based on results of previous factor analyses conducted on the same dataset. These food groups included fruits, vegetables, legumes, olive oil, burghol, dairy products, starchy vegetables, dried fruits, and eggs. Using Pearson’s correlation and scores tertiles distributions agreement, the derived LMD index was compared to previously published EMD indexes from Greece, Spain, Italy, France, and EPIC. Results: Fruits, vegetables and olive oil were common denominators to all MD scores. Food groups, specific to the LMD, included burghol and dried fruits. The LMD score significantly correlated with the EMD scores, while being closest to the Italian (r=0.57) and farthest from the French (r=0.21). Percent agreement between scores’ tertile distributions and Kappa statistics confirmed these findings. Multivariate linear regression showed that older age, higher educational, female gender, and healthy lifestyle characteristics were associated with increased adherence to all MD studied. Conclusion: A novel LMD index was proposed to characterize Mediterranean diet in Lebanon, complementing international efforts to characterize the MD and its association with disease risk.

Keywords: mediterranean diet, adherence, Middle-East, Lebanon, Europe

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Authors: Martin Juckel

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Probably no other field of inorganic chemistry has undergone such a rapid development in the past two decades than the low oxidation state chemistry of main group elements. This rapid development has only been possible by the development of new bulky ligands. In case of our research group, super-bulky monodentate amido ligands and β-diketiminate ligands have been used to a great success. We first synthesized the unprecedented magnesium(I) dimer [ᴹᵉˢNacnacMg]₂ (ᴹᵉˢNacnac = [(ᴹᵉˢNCMe)₂CH]-; Mes = mesityl, which has since been used both as reducing agent and also for the synthesis of new metal-magnesium bonds. In case of the zinc bromide precursor [L*ZnBr] (L*=(N(Ar*)(SiPri₃); (Ar* = C₆H₂{C(H)Ph₂}₂Me-2,6,4, the reduction with [ᴹᵉˢNacnacMg]₂ led to such a metal-magnesium bond. This [L*ZnMg(ᴹᵉˢNacnac)] compound can be seen as an ‘inorganic Grignard reagent’, which can be used to transfer the metal fragment onto other functional groups or other metal centers; just like the conventional Grignard reagent. By simple addition of (TBoN)GeCl (TBoN = N(SiMe₃){B(DipNCH)₂) to the aforesaid compound, we were able to transfer the amido-zinc fragment to the Ge center of the germylene starting material and to synthesize the first example of a germanium(II)-zinc bond: [:Ge(TBoN)(ZnL*)]. While these reactions typically led to complex product mixture, [:Ge(TBoN)(ZnL*)] could be isolated as dark blue crystals in a good yield. This new compound shows interesting reactivity towards small molecules, especially dihydrogen gas. This is of special interest as dihydrogen is one of the more difficult small molecules to activate, due to its strong (BDE = 108 kcal/mol) and non-polar bond. In this context, the interaction between H₂ σ-bond with the tetrelylene p-Orbital (LUMO), with concomitant donation of the tetrelylene lone pair (HOMO) into the H₂ σ* orbital are responsible for the activation of dihydrogen gas. Accordingly, the narrower the HOMO-LUMO gap of tertelylene, the more reactivity towards H₂ it typically is. The aim of a narrow HOMO-LUMO gap was reached by transferring electropositive substituents respectively metal substituents with relatively low Pauling electronegativity (zinc: 1.65) onto the Ge center (here: the zinc-amido fragment). In consideration of the unprecedented reactivity of [:Ge(TBoN)(ZnL*)], a computational examination of its frontier orbital energies was undertaken. The energy separation between the HOMO, which has significant Ge lone pair character, and the LUMO, which has predominantly Ge p-orbital character, is narrow (40.8 kcal/mol; cf.∆S-T= 24.8 kcal/mol), and comparable to the HOMO-LUMO gaps calculated for other literature known complexes). The calculated very narrow HOMO-LUMO gap for the [:Ge(TBoN)(ZnL*)] complex is consistent with its high reactivity, and is remarkable considering that it incorporates a π-basic amide ligand, which are known to raise the LUMO of germylenes considerably.

Keywords: activation of dihydrogen gas, narrow HOMO-LUMO gap, first germanium(II)-zinc bond, inorganic Grignard reagent

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Authors: Mohammadreza Sedighi, Mohammad Said Saidi, Hesamoddin Salarian

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A numerical study has been performed to investigate the effect of using different turbulent models on natural convection flow field and temperature distributions in partially heated square cavity compare to benchmark. The temperature of the right vertical wall is lower than that of heater while other walls are insulated. The commercial CFD codes are used to model. Standard k-w model provided good agreement with the experimental data.

Keywords: Buoyancy, Cavity, CFD, Heat Transfer, Natural Convection, Turbulence

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Authors: Shweta Verma

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Background: Epilepsy is a chronic non-communicable central nervous system (CNS) disorder which affects a large population of all ages. Different classes of drugs are used for the treatment of this neurological disorder, but due to augmented drug resistance and side effects, these drugs become incompetent. Therefore, we design the synthesis of ten new derivatives of Phenytoin. The moiety of Phenytoin was hybridized with different phenols by using three step approach. The synthesized molecules were then investigated for different physicochemical parameters, such as Log P values using diverse software programs and to predict the potential to cross the blood-brain barrier. Objective: The Phenytoin derivatives were designed, synthesized, and characterized to meet the structural necessities indispensable for antiepileptic activity. Method: Firstly, the chloroacetylation of the 5,5-diphenyl hydantoin was carried out, and then various substituted phenols were added to it. The synthesized compounds were characterized and evaluated for antianxiety activity by elevated plus maze method and antiepileptic activity by using subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) models and neurotoxicity. Result: The number of derivatives of 5,5-diphenyl hydantoin was developed and optimized. The number of parameters was optimized which reveal that the compound containing chloro group such as C3 and C6 showed imperative potential when compared with the standard drug Diazepam. Other compounds containing nitro and methyl group were also found to possess activity. Conclusion: It was summarized that the new compounds of 5,5-diphenyl hydantoin derivatives were synthesized. The results of the data show that the compound containing chloro group is more potent for CNS activity. The new compounds have the probability of being optimized further to engender new scaffolds to treat various CNS disorders.

Keywords: phenytoin, parameters, CNS activity, blood-brain barrier, Log P, CNS active

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Authors: Rashad A. Al-Salahi, Mohamed S. Marzouk

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Aiming to the synthesis of bioactive triazoloquinazolines, a new series of 2-(methylthio)benzo [g]-[1,2,4] triazolo [1,5-a] quinazolin-5(4H)-ones was synthesized from 2-(methylthio)benzo [g]-[1,2,4] triazolo [1,5-a] quinazolin-5(4H)-one. All synthesized derivatives based on N-alkylation and chlorination of the parent compound and its salfonyl derivative. The success of the reactions was proved by NMR, IR, and HREI-MS analyses for all products.

Keywords: triazoloquinazoline, alkylation, thionation, quinazolin

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Authors: Muhammad A. Muhammad

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Butenafine (N-4-tert-butyl benzyl-N-methyl-1-naphthylene methylamine hydrochloride) is a benzylamine antimycotic (antifungal) agent that has a broad spectrum of action. The quest for improved antimycotic action brought about many research on the structure-activity properties of butenafine in relation to other antifungal agents. Of all those research, only little or no effort was recorded on the substituents attached to the aromatic systems in butenafine. In this research, N-(4-(tert-butyl) benzyl)-1-(4-tert-butyl) phenyl)-N-methyl methanaminium chloride, which is a butenafine analogue was synthesised from tert-butyl benzyl derivatives, by reductive amination using various solvents through a direct approach, where 1,2-dichloroethane gave the best solvent action at 40 °C (Yield: 75%) and of all the reducing agents used, sodium borohydride was found to give the best reducing action in the presence of silica chloride at room temperature (Yield: 50%). Characterization of the compound by 1H NMR showed a singlet peak of 18 hydrogen atoms with a chemical shift at 1.3-1.5 ppm for the presence of 6 methyl groups in the two tert-butyl substituents, the 13C NMR also indicated the presence of the two tert-butyl substituents by the peak with a chemical shift at 31-32 ppm for the six methyl carbon atoms, the IR indicated the presence of a tertiary ammonium ion by a strong band at 2460 cm-1 and finally the EIS-MS confirmed the molar mass of the compound by a mass to charge ratio of 324.2693. These results suggested that the target molecule was actually synthesised and therefore, 1,2-dichloroethane is a good solvent for this synthesis, and the most suitable reducing agent is sodium borohydride.

Keywords: antimicrobial agents, antimycotic agents, butenafine, chemotherapeutic agents, semisynthetic agents

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Authors: Md. Asif Ullah, M. A. R. Sarkar

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This paper illustrates 2-D and 3-D simulations of sub-channels of a Pressurized Water Reactor (PWR) having hexagonal array of fuel rods. At a steady state, the temperature of outer surface of the cladding of fuel rod is kept about 1200°C. The temperature of this isothermal surface is taken as boundary condition for simulation. Water with temperature of 290°C is given as a coolant inlet to the primary water circuit which is pressurized upto 157 bar. Turbulent flow of pressurized water is used for heat removal. In 2-D model, temperature, velocity, pressure and Nusselt number distributions are simulated in a vertical sectional plane through the sub-channels of a hexagonal fuel rod assembly. Temperature, Nusselt number and Y-component of convective heat flux along a line in this plane near the end of fuel rods are plotted for different Reynold’s number. A comparison between X-component and Y-component of convective heat flux in this vertical plane is analyzed. Hexagonal fuel rod assembly has three types of sub-channels according to geometrical shape whose boundary conditions are different too. In 3-D model, temperature, velocity, pressure, Nusselt number, total heat flux magnitude distributions for all the three sub-channels are studied for a suitable Reynold’s number. A horizontal sectional plane is taken from each of the three sub-channels to study temperature, velocity, pressure, Nusselt number and convective heat flux distribution in it. Greater values of temperature, Nusselt number and Y-component of convective heat flux are found for greater Reynold’s number. X-component of convective heat flux is found to be non-zero near the bottom of fuel rod and zero near the end of fuel rod. This indicates that the convective heat transfer occurs totally along the direction of flow near the outlet. As, length to radius ratio of sub-channels is very high, simulation for a short length of the sub-channels are done for graphical interface advantage. For the simulations, Turbulent Flow (K-Є ) module and Heat Transfer in Fluids (ht) module of COMSOL MULTIPHYSICS 5.0 are used.

Keywords: sub-channels, Reynold’s number, Nusselt number, convective heat transfer

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Authors: Michalina Aniola, Andrzej Katrusiak

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4,4-Bipyridine is an important compound often used in chemical practice and more recently frequently applied for designing new metal organic framework (MoFs). Here we present a systematic high-pressure study of its hydrobromide salt. 4,4-Bipyridine hydrobromide monohydrate, 44biPyHBrH₂O, at ambient-pressure is orthorhombic, space group P212121 (phase a). Its hydrostatic compression shows that it is stable to 1.32 GPa at least. However, the recrystallization above 0.55 GPa reveals a new hidden b-phase (monoclinic, P21/c). Moreover, when the 44biPyHBrH2O is heated to high temperature the chemical reactions of this compound in methanol solution can be observed. High-pressure experiments were performed using a Merrill-Bassett diamond-anvil cell (DAC), modified by mounting the anvils directly on the steel supports, and X-ray diffraction measurements were carried out on a KUMA and Excalibur diffractometer equipped with an EOS CCD detector. At elevated pressure, the crystal of 44biPyHBrH₂O exhibits several striking and unexpected features. No signs of instability of phase a were detected to 1.32 GPa, while phase b becomes stable at above 0.55 GPa, as evidenced by its recrystallizations. Phases a and b of 44biPyHBrH2O are partly isostructural: their unit-cell dimensions and the arrangement of ions and water molecules are similar. In phase b the HOH-Br- chains double the frequency of their zigzag motifs, compared to phase a, and the 44biPyH+ cations change their conformation. Like in all monosalts of 44biPy determined so far, in phase a the pyridine rings are twisted by about 30 degrees about bond C4-C4 and in phase b they assume energy-unfavorable planar conformation. Another unusual feature of 44biPyHBrH2O is that all unit-cell parameters become longer on the transition from phase a to phase b. Thus the volume drop on the transition to high-pressure phase b totally depends on the shear strain of the lattice. Higher temperature triggers chemical reactions of 44biPyHBrH2O with methanol. When the saturated methanol solution compound precipitated at 0.1 GPa and temperature of 423 K was required to dissolve all the sample, the subsequent slow recrystallization at isochoric conditions resulted in disalt 4,4-bipyridinium dibromide. For the 44biPyHBrH2O sample sealed in the DAC at 0.35 GPa, then dissolved at isochoric conditions at 473 K and recrystallized by slow controlled cooling, a reaction of N,N-dimethylation took place. It is characteristic that in both high-pressure reactions of 44biPyHBrH₂O the unsolvated disalt products were formed and that free base 44biPy and H₂O remained in the solution. The observed reactions indicate that high pressure destabilized ambient-pressure salts and favors new products. Further studies on pressure-induced reactions are carried out in order to better understand the structural preferences induced by pressure.

Keywords: conformation, high-pressure, negative area compressibility, polymorphism

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Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

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Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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Authors: Gajanan M. Sonwane

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The computational studies on 2-phenazinamines with their protein targets have been carried out to design compounds with potential anticancer activity. This strategy of designing compounds possessing selectivity over specific tyrosine kinase has been achieved through G-QSAR and molecular docking studies. The objective of this research has been to design newer 2-phenazinamine derivatives as Bcr-Abl tyrosine kinase inhibitors by G-QSAR, molecular docking studies followed by wet-lab studies along with evaluation of their anticancer potential. Computational chemistry was done by using VLife MDS 4.3 and Autodock 4.2 followed by wet-lab experiments for synthesizing 2-phenazinamine derivatives. The chemical structures of ligands in 2D were drawn by employing Chemdraw 2D Ultra 8.0 and were converted into 3D. These were optimized by using a semi-empirical method called MOPAC. The protein structure was retrieved from RCSC protein data bank as a PDB file. The binding interactions of protein and ligands were done by using PYMOL. The molecular properties of the designed compounds were predicted in silico by using Osiris property explorer. The parent compound 2-phenazinamine was synthesized by reduction of 2, 4-dinitro-N-phenyl-benzenamine in the presence of tin chloride followed by cyclization in the presence of nitrobenzene and magnesium sulfate. The derivatization at the amino function of 2-phenazinamine was performed by treating parent compound with various aldehydes in the presence of dicyclohexylcarbodiimide (DCC) and urea to afford 2-(2-chlorophenyl)-3-(phenazine-2-yl) thiazolidine-4-one. Synthesized 39 novel derivatives of 2-phenazinamine and performed antioxidant activity, anti antiproliferative on the bulb of onion and anticancer activity on cell line showing significant competition with marked blockbuster drug imatinib.

Keywords: computer-aided drug design, tyrosin kinases, anticancer, docking

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Authors: Petr Jizba, Jan Korbel

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We combine an axiomatics of Rényi with the q-deformed version of Khinchin axioms to obtain a measure of information (i.e., entropy) which accounts both for systems with embedded self-similarity and non-extensivity. We show that the entropy thus obtained is uniquely solved in terms of a one-parameter family of information measures. The ensuing maximal-entropy distribution is phrased in terms of a special function known as the Lambert W-function. We analyze the corresponding ‘high’ and ‘low-temperature’ asymptotics and reveal a non-trivial structure of the parameter space.

Keywords: multifractals, Rényi information entropy, THC entropy, MaxEnt, heavy-tailed distributions

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Authors: Rozalina Keremedchieva, Ivan Svinyarov, Milen G. Bogdanov

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In continuation of a research project on the application of ionic liquids (ILs) as an alternative to the conventional organic solvents used in the recovery of value added chemicals of industrial interest1-3 we developed a procedure for back extraction and isolation in pure form of the biologically active alkaloid glaucine from IL-based aqueous solutions. One of the approaches applied was the formation of two-phase systems (IL-ATPS) by the addition of kosmotropic salts to the plant extract. The ability of the salts (Na2CO3, MgSO4, (NH4)2SO4, NaH2PO4) to induce the formation of two-phase systems and the influence of pH value on the partition coefficients of glaucine was comprehensively studied. As a result, it was found that the target alkaloid is preferably partitioned into the IL-rich phase regardless of the pH value of the medium and thus shows the inapplicability of the approach used for the isolation of the target compound from the ionic liquid. However, the results obtained can be used as a platform for the development of an analytical method for the quantitative determination of low concentrations of glaucine in biological samples. We further examined the ability of a series of organic solvents such as diethyl ether, Tert-butylmethyl ether, ethyl acetate, butyl acetate, toluene, chloroform, dichloromethane to recover glaucine form raw IL-based aqueous extracts. Optimal conditions for quantitative extraction of glaucine into chloroform were found from which, after removal of the solvent and subsequent recrystallization from ethanol, the target compound was isolated in a high purity as a hydrobromide salt – The form in which it entrance as an active ingredient in various medicines.

Keywords: natural products, ionic liquids, solid-liquid extraction, liquid-liquid extraction

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Authors: S. I. Usenko, V. N. Golubeva, I. A. Konopkina, I. V. Astakhova, O. V. Vakhnina, A. A. Korableva, A. A. Kalinina, K. B. Zhogova

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Gold can be determined in natural objects and manufactured articles of different origin. The up-to-date status of research and problems of high gold level determination in alloys and manufactured articles are described in detail in the literature. No less important is the task of this metal determination in minerals, process products and waste pieces. The latters, as objects of gold content chemical analysis, are most hard-to-study for two reasons: Because of high requirements to accuracy of analysis results and because of difference in chemical and phase composition. As a rule, such objects are characterized by compound, variable and very often unknown matrix composition that leads to unpredictable and uncontrolled effect on accuracy and other analytical characteristics of analysis technique. In this paper, the methods for the determination of gold are described, using flame atomic-absorption spectrophotometry and gravimetric analysis technique. The techniques are aimed at gold determination in a solution for gold etching (KJ+J2), in the technological mixture formed after cleaning stainless steel members of vacuum-deposit installation with concentrated nitric and hydrochloric acids as well as in gold-containing powder resulted from liquid wastes reprocessing. Optimal conditions for sample preparation and analysis of liquid and solid waste specimens of compound and variable matrix composition were chosen. The boundaries of relative resultant error were determined for the methods within the range of gold mass concentration from 0.1 to 30g/dm3 in the specimens of liquid wastes and mass fractions from 3 to 80% in the specimens of solid wastes.

Keywords: microelectronics waste pieces, gold, sample preparation, atomic-absorption spectrophotometry, gravimetric analysis technique

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Authors: Dalvir Kataria, Khushminder Kaur Chahal, Amit Kumar

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The carrot seed essential oil was obtained by hydrodistillation. Hexane, dichloromethane, and methanol solvents were used for extraction of carrot seed by Soxhlet extraction methods. The major and minor compounds identified in carrot seed essential oil were carotol (52.73), daucol (5.10), daucene (5.68), (E)-β-farnesene (5.40), β-cubebene (3.19), longifolenaldehyde (3.23), β-elimene (3.23), (E)-caryophyllene (1.22), β-bisabolene (2.95) etc. The chemical composition of hexane, dichloromethane, and methanol extracts was different. Carotol was the common compound present. Major compounds isolated were from the carrot seed essential oil by column chromatography. Chemical transformations of carotol (2) with mercuric acetate/sodium borohydride, dry hydrochloric acid gas, acetonitrile/sulfuric acid, selenium dioxide/t-butyl hydrogen peroxide, N-bromosuccinimide, hydrogen iodide, and phenol were carried out. The derivatives of carotol were designed to explore the significance of some structural modifications in relation to antioxidant activities. The structures of major compounds and derivatives were confirmed on the basis of FT-IR, 1HNMR and 13CNMR spectroscopy. Antioxidant activity of carrot seed essential oil, various extracts and isolated compounds were tested by in vitro models involving 2, 2-diphenyl-1-picrylhydrazyl (DPPH•), hydroxyl (OH•), nitric oxide (NO•), superoxide radical scavenging methods and ferric reducing antioxidant power assay (FRAP). Chemical transformations of major isolated compound carotol were carried out, and antioxidant activity of all compounds was undertaken. The major sesquiterpenoidcarotol isolated from carrot seed essential oil showed the highest antioxidant activity in all the methods. The methanol extract showed higher antioxidant potential as compared to carrot seed essential oil, hexane, and dichloromethane extracts.

Keywords: antioxidant, carotol, carrot, DPPH

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Authors: Amir Asadi, Karim Habib, Robert J. Moon, Kyriaki Kalaitzidou

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There has been considerable interest in cellulose nanomaterials (CN) as polymer and polymer composites reinforcement due to their high specific modulus and strength, low density and toxicity, and accessible hydroxyl side groups that can be readily chemically modified. The focus of this study is making lightweight composites for better fuel efficiency and lower CO2 emission in auto industries with no compromise on mechanical performance using a scalable technique that can be easily integrated in sheet molding compound (SMC) manufacturing lines. Light weighting will be achieved by replacing part of the heavier components, i.e. glass fibers (GF), with a small amount of cellulose nanocrystals (CNC) in short GF/epoxy composites made using SMC. CNC will be introduced as coating of the GF rovings prior to their use in the SMC line. The employed coating method is similar to the fiber sizing technique commonly used and thus it can be easily scaled and integrated to industrial SMC lines. This will be an alternative route to the most techniques that involve dispersing CN in polymer matrix, in which the nanomaterials agglomeration limits the capability for scaling up in an industrial production. We have demonstrated that incorporating CNC as a coating on GF surface by immersing the GF in CNC aqueous suspensions, a simple and scalable technique, increases the interfacial shear strength (IFSS) by ~69% compared to the composites produced by uncoated GF, suggesting an enhancement of stress transfer across the GF/matrix interface. As a result of IFSS enhancement, incorporation of 0.17 wt% CNC in the composite results in increases of ~10% in both elastic modulus and tensile strength, and 40 % and 43 % in flexural modulus and strength respectively. We have also determined that dispersing 1.4 and 2 wt% CNC in the epoxy matrix of short GF/epoxy SMC composites by sonication allows removing 10 wt% GF with no penalty on tensile and flexural properties leading to 7.5% lighter composites. Although sonication is a scalable technique, it is not quite as simple and inexpensive as coating the GF by passing through an aqueous suspension of CNC. In this study, the above findings are integrated to 1) investigate the effect of CNC content on mechanical properties by passing the GF rovings through CNC aqueous suspension with various concentrations (0-5%) and 2) determine the optimum ratio of the added CNC to the removed GF to achieve the maximum possible weight reduction with no cost on mechanical performance of the SMC composites. The results of this study are of industrial relevance, providing a path toward producing high volume lightweight and mechanically enhanced SMC composites using cellulose nanomaterials.

Keywords: cellulose nanocrystals, light weight polymer-matrix composites, mechanical properties, sheet molding compound (SMC)

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Yiyuan Tao

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Under the impact of global warming together with the intensification of human activities, the hydrological regimes may be altered, and the traditional stationary assumption was no longer satisfied. However, most of the current design standards of water infrastructures were still based on the hypothesis of stationarity, which may inevitably result in severe biases. Many critical impacts of climate on ecosystems, society, and the economy are controlled by extreme events rather than mean values. Therefore, it is of great significance to identify the non-stationarity of precipitation extremes and model the precipitation extremes in a nonstationary framework. The Wei River Basin (WRB), located in a continental monsoon climate zone in China, is selected as a case study in this study. Six extreme precipitation indices were employed to investigate the changing patterns and stationarity of precipitation extremes in the WRB. To identify if precipitation extremes are stationary, the Mann-Kendall trend test and the Pettitt test, which is used to examine the occurrence of abrupt changes are adopted in this study. Extreme precipitation indices series are fitted with non-stationary distributions that selected from six widely used distribution functions: Gumbel, lognormal, Weibull, gamma, generalized gamma and exponential distributions by means of the time-varying moments model generalized additive models for location, scale and shape (GAMLSS), where the distribution parameters are defined as a function of time. The results indicate that: (1) the trends were not significant for the whole WRB, but significant positive/negative trends were still observed in some stations, abrupt changes for consecutive wet days (CWD) mainly occurred in 1985, and the assumption of stationarity is invalid for some stations; (2) for these nonstationary extreme precipitation indices series with significant positive/negative trends, the GAMLSS models are able to capture well the temporal variations of the indices, and perform better than the stationary model. Finally, the differences between the quantiles of nonstationary and stationary models are analyzed, which highlight the importance of nonstationary modeling of precipitation extremes in the WRB.

Keywords: extreme precipitation, GAMLSSS, non-stationary, Wei River Basin

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Authors: Jian-Heng Wu, Bor-Shen Lin

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The temperature-salinity relationship is one of the most important characteristics used for identifying water masses in marine research. Temperature-salinity characteristics, however, may change dynamically with respect to the geographic location and is quite sensitive to the depth at the same location. When depth is taken into consideration, however, it is not easy to compare the characteristics of different water masses efficiently for a wide range of areas of the ocean. In this paper, the Gaussian mixture model was proposed to analyze the temperature-salinity-depth characteristics of water masses, based on which comparison between water masses may be conducted. Gaussian mixture model could model the distribution of a random vector and is formulated as the weighting sum for a set of multivariate normal distributions. The temperature-salinity-depth data for different locations are first used to train a set of Gaussian mixture models individually. The distance between two Gaussian mixture models can then be defined as the weighting sum of pairwise Bhattacharyya distances among the Gaussian distributions. Consequently, the distance between two water masses may be measured fast, which allows the automatic and efficient comparison of the water masses for a wide range area. The proposed approach not only can approximate the distribution of temperature, salinity, and depth directly without the prior knowledge for assuming the regression family, but may restrict the complexity by controlling the number of mixtures when the amounts of samples are unevenly distributed. In addition, it is critical for knowledge discovery in marine research to represent, manage and share the temperature-salinity-depth characteristics flexibly and responsively. The proposed approach has been applied to a real-time visualization system of ocean data, which may facilitate the comparison of water masses by aggregating the data without degrading the discriminating capabilities. This system provides an interface for querying geographic locations with similar temperature-salinity-depth characteristics interactively and for tracking specific patterns of water masses, such as the Kuroshio near Taiwan or those in the South China Sea.

Keywords: water mass, Gaussian mixture model, data visualization, system framework

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Authors: D. Sigirli

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The Receiver Operating Characteristic (ROC) curve is a commonly used statistical tool for evaluating the diagnostic performance of screening and diagnostic test with continuous or ordinal scale results which aims to predict the presence or absence probability of a condition, usually a disease. When the test results were measured as numeric values, sensitivity and specificity can be computed across all possible threshold values which discriminate the subjects as diseased and non-diseased. There are infinite numbers of possible decision thresholds along the continuum of the test results. The ROC curve presents the trade-off between sensitivity and the 1-specificity as the threshold changes. The empirical ROC curve which is a non-parametric estimator of the ROC curve is robust and it represents data accurately. However, especially for small sample sizes, it has a problem of variability and as it is a step function there can be different false positive rates for a true positive rate value and vice versa. Besides, the estimated ROC curve being in a jagged form, since the true ROC curve is a smooth curve, it underestimates the true ROC curve. Since the true ROC curve is assumed to be smooth, several smoothing methods have been explored to smooth a ROC curve. These include using kernel estimates, using log-concave densities, to fit parameters for the specified density function to the data with the maximum-likelihood fitting of univariate distributions or to create a probability distribution by fitting the specified distribution to the data nd using smooth versions of the empirical distribution functions. In the present paper, we aimed to propose a smooth ROC curve estimation based on the boundary corrected kernel function and to compare the performances of ROC curve smoothing methods for the diagnostic test results coming from different distributions in different sample sizes. We performed simulation study to compare the performances of different methods for different scenarios with 1000 repetitions. It is seen that the performance of the proposed method was typically better than that of the empirical ROC curve and only slightly worse compared to the binormal model when in fact the underlying samples were generated from the normal distribution.

Keywords: empirical estimator, kernel function, smoothing, receiver operating characteristic curve

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Authors: O. V. Vyazovska

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Behavioral efficiency is one of the main principles to be successful in nature. Accuracy of visual discrimination is determined by the attention, learning experience, and memory. In the experimental condition, pigeons’ responses to visual stimuli presented on the screen of the monitor are behaviorally manifested by pecking or not pecking the stimulus, by the number of pecking, reaction time, etc. The higher the probability of rewarding is, the more likely pigeons will respond to the stimulus. We trained 8 pigeons (Columba livia) on a stagewise go/no-go visual discrimination task.16 visual stimuli were created from all possible combinations of four binary dimensions: brightness (dark/bright), size (large/small), line orientation (vertical/horizontal), and shape (circle/square). In the first stage, we presented S+ and 4 S-stimuli: the first that differed in all 4-dimensional values from S+, the second with brightness dimension sharing with S+, the third sharing brightness and orientation with S+, the fourth sharing brightness, orientation and size. Then all 16 stimuli were added. Pigeons rejected correctly 6-8 of 11 new added S-stimuli at the beginning of the second stage. The results revealed that pigeons’ behavior at the beginning of the second stage was controlled by probabilities of rewarding for 4 dimensions learned in the first stage. More or fewer mistakes with dimension discrimination at the beginning of the second stage depended on the number S- stimuli sharing the dimension with S+ in the first stage. A significant inverse correlation between the number of S- stimuli sharing dimension values with S+ in the first stage and the dimensional learning rate at the beginning of the second stage was found. Pigeons were more confident in discrimination of shape and size dimensions. They made mistakes at the beginning of the second stage, which were not associated with these dimensions. Thus, the received results help elucidate the principles of dimensional stimulus control during learning compound multidimensional visual stimuli.

Keywords: visual go/no go discrimination, selective attention, dimensional stimulus control, pigeon

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Authors: Howaida I. Abd-Alla, Amal Z. Hassan, Maha Soltan, Atef G. Hanna, Mounir M. El-Safty

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Acokanthera oblongifolia (Apocynaceae) is used for treatment of several infection diseases and is a well-known cardiac glycoside-containing plant. The infusion of their leaves is gargled to treat tonsillitis and is used medicinally to treat snakebites. The total cardiac glycosides content in the leaves was determined by referring to gitoxigenin as a reference compound. Two triterpenes, lup-20(29)-en-3β-ol (1) and oleanolic acid (2); two cardenolides, acovenoside A (3) and acobioside A (4) were isolated from the ethyl acetate extract. Their structures were determined on the basis of spectral analysis. Major constituents isolated from this species were evaluated for cytotoxicity against normal lung cell line (Wi38) and antimicrobial activities against Gram-positive (two strains) and Gram-negative bacteria (four strains), yeast-like fungi (two strains) and fungi (five strains). The minimum inhibitory concentration (MIC) of the compounds was determined using broth microdilution method. Their viral inhibitory effects against avian influenza virus type A (AI-H5N1) and Newcastle disease virus (NDV) in specific pathogen free (SPF) embryonated chicken eggs (ECE), chicken embryo fibroblasts (CEF) and Vero cells were evaluated. The cardenolide (3) showed viral inhibitory effects against AI-H5N1 and NDV in SPF ECE. The two cardenolides isolated have shown potent cytotoxicity against Vero cells. Compound (3) showed potent anti-Gram-negative bacteria activity. These results suggested that acovenoside A might be promising for future antiviral and antimicrobial drug design.

Keywords: Acokanthera, AI-H5N1, Cardenolides, NDV, SPF-ECE, VERO, Wi38 , Microbe

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Authors: Jian-Jun Shu

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A cold, thin film of liquid impinging on an isothermal hot, horizontal surface has been investigated. An approximate solution for the velocity and temperature distributions in the flow along the horizontal surface is developed, which exploits the hydrodynamic similarity solution for thin film flow. The approximate solution may provide a valuable basis for assessing flow and heat transfer in more complex settings.

Keywords: flux, free impinging jet, solid-surface, uniform wall temperature

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Authors: Mohamed Basheer Abdul Atti Hassan

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This research paper will follow the main outlines of the Italian colonization in Libya in a historical geopolitical approach; before we reach the contemporary map. In this study, we are also concerned with following the chain's links, not as drama in time, but as a strategy in place, so that it draws to us a map of power and the distribution of political formations throughout this period within and around Libya. From the sum of these variable distributions and successive balances, we can come up with the basic principles that determined the Italian history in Libya and formed its political entity, which is a compass of guidance and an indication of the future.

Keywords: conflict, Mediterranean, colonization, political history

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Authors: Augustas Vaitkevicius, Mikhail Korjik, Eugene Tretyak, Ekaterina Trusova, Gintautas Tamulaitis

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Silicate materials are widely used as luminescent materials in amorphous and crystalline phase. Lithium silicate glass is popular for making neutron sensitive scintillation glasses. Cerium-doped single crystalline silicates of rare earth elements and yttrium have been demonstrated to be good scintillation materials. Due to their high thermal and photo-stability, silicate glass ceramics are supposed to be suitable materials for producing light converters for high power white light emitting diodes. In this report, the influence of glass composition and crystallization on photoluminescence (PL) of different silicate glasses was studied. Barium (BaO-2SiO₂) and lithium (Li₂O-2SiO₂) glasses were under study. Cerium, dysprosium, erbium and europium ions as well as their combinations were used for doping. The influence of crystallization was studied after transforming the doped glasses into glass ceramics by heat treatment in the temperature range of 550-850 degrees Celsius for 1 hour. The study was carried out by comparing the photoluminescence (PL) spectra, spatial distributions of PL parameters and quantum efficiency in the samples under study. The PL spectra and spatial distributions of their parameters were obtained by using confocal PL microscopy. A WITec Alpha300 S confocal microscope coupled with an air cooled CCD camera was used. A CW laser diode emitting at 405 nm was exploited for excitation. The spatial resolution was in sub-micrometer domain in plane and ~1 micrometer perpendicularly to the sample surface. An integrating sphere with a xenon lamp coupled with a monochromator was used to measure the external quantum efficiency. All measurements were performed at room temperature. Chromatic properties of the light emission from the glasses and glass ceramics have been evaluated. We observed that the quantum efficiency of the glass ceramics is higher than that of the corresponding glass. The investigation of spatial distributions of PL parameters revealed that heat treatment of the glasses leads to a decrease in sample homogeneity. In the case of BaO-2SiO₂: Eu, 10 micrometer long needle-like objects are formed, when transforming the glass into glass ceramics. The comparison of PL spectra from within and outside the needle-like structure reveals that the ratio between intensities of PL bands associated with Eu²⁺ and Eu³⁺ ions is larger in the bright needle-like structures. This indicates a higher degree of crystallinity in the needle-like objects. We observed that the spectral positions of the PL bands are the same in the background and the needle-like areas, indicating that heat treatment imposes no significant change to the valence state of the europium ions. The evaluation of chromatic properties confirms applicability of the glasses under study for fabrication of white light sources with high thermal stability. The ability to combine barium and lithium glass matrixes and doping by Eu, Ce, Dy, and Tb enables optimization of chromatic properties.

Keywords: glass ceramics, luminescence, phosphor, silicate

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Authors: R. Kiruthika, A. Kannan

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Steganography is the problem of hiding secret messages in 'innocent – looking' public communication so that the presence of the secret message cannot be detected. This paper introduces a steganographic security in terms of computational in-distinguishability from a channel of probability distributions on cover messages. This method first splits the cover image into two separate blocks using Douglas – Peucker algorithm. The text message and the image will be hided in the Least Significant Bit (LSB) of the cover image.

Keywords: steganography, lsb, embedding, Douglas-Peucker algorithm

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Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

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According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

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Authors: Tong-Hsien Chow

Abstract:

Background: Plantar pressure measurement is an effective method for assessing plantar loading and can be applied to evaluating movement performance of the foot. The purpose of this study is to explore the sprint athletes’ plantar loading characteristics and pain profiles in static standing. Methods: Experiments were undertaken on 80 first-division college sprint athletes and 85 healthy non-sprinters. ‘JC Mat’, the optical plantar pressure measurement was applied to examining the differences between both groups in the arch index (AI), three regional and six distinct sub-regional plantar pressure distributions (PPD), and footprint characteristics. Pain assessment and self-reported health status in sprint athletes were examined for evaluating their common pain areas. Results: Findings from the control group, the males’ AI fell into the normal range. Yet, the females’ AI was classified as the high-arch type. AI values of the sprint group were found to be significantly lower than the control group. PPD were higher at the medial metatarsal bone of both feet and the lateral heel of the right foot in the sprint group, the males in particular, whereas lower at the medial and lateral longitudinal arches of both feet. Footprint characteristics tended to support the results of the AI and PPD, and this reflected the corresponding pressure profiles. For the sprint athletes, the lateral knee joint and biceps femoris were the most common musculoskeletal pains. Conclusions: The sprint athletes’ AI were generally classified as high arches, and that their PPD were categorized between the features of runners and high-arched runners. These findings also correspond to the profiles of patellofemoral pain syndrome (PFPS)-related plantar pressure. The pain profiles appeared to correspond to the symptoms of high-arched runners and PFPS. The findings reflected upon the possible link between high arches and PFPS. The correlation between high-arched runners and PFPS development is worth further studies.

Keywords: sprint athletes, arch index, plantar pressure distributions, high arches, patellofemoral pain syndrome

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Authors: Strahinja Kovačević, Sanja Podunavac-Kuzmanović, Lidija Jevrić, Cristina Prandi, Piermichele Kobauri

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The present study is based on molecular modeling of a series of twelve 5-(4-substituent-phenoxy)-3-methylfuran-2(5H)-one derivatives which have potential of strigolactones mimics toward Striga hermonthica. The first step of the analysis included the calculation of molecular descriptors which numerically describe the structures of the analyzed compounds. The descriptors ALOGP (lipophilicity), AClogS (water solubility) and BBB (blood-brain barrier penetration), served as the input variables in multiple linear regression (MLR) modeling of germination activity toward S. hermonthica. Two MLR models were obtained. The first MLR model contains ALOGP and AClogS descriptors, while the second one is based on these two descriptors plus BBB descriptor. Despite the braking Topliss-Costello rule in the second MLR model, it has much better statistical and cross-validation characteristics than the first one. The ALOGP and AClogS descriptors are often very suitable predictors of the biological activity of many compounds. They are very important descriptors of the biological behavior and availability of a compound in any biological system (i.e. the ability to pass through the cell membranes). BBB descriptor defines the ability of a molecule to pass through the blood-brain barrier. Besides the lipophilicity of a compound, this descriptor carries the information of the molecular bulkiness (its value strongly depends on molecular bulkiness). According to the obtained results of MLR modeling, these three descriptors are considered as very good predictors of germination activity of the analyzed compounds toward S. hermonthica seeds. This article is based upon work from COST Action (FA1206), supported by COST (European Cooperation in Science and Technology).

Keywords: chemometrics, germination activity, molecular modeling, QSAR analysis, strigolactones

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Authors: Norhan H. Mahdally, Bathini Thissera Riham A. ElShiekh, Noha M. Elhosseiny, Mona T. Kashef, Ali M. El Halawany, Mostafa E. Rateb, Ahmed S. Attia

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Multidrug-resistant (MDR) pathogens pose a global threat to healthcare settings. The exhaustion of the current antibiotic arsenal and the scarcity of new antimicrobials in the pipeline aggravate this threat and necessitate a prompt and effective response. This study focused on two major pathogens that can cause serious infections: carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA). Multiple soil isolates were collected from several locations throughout Egypt and screened for their conventional and non-conventional antimicrobial activities against MDR pathogens. One isolate exhibited potent antimicrobial activity and was subjected to multiple rounds of fractionation. After fermentation and bio-guided fractionation, we identified pure microbial secondary metabolites with two scaffolds that exhibited promising effects against CRAB and MRSA. Scaling up and chemical synthesis of derivatives of the identified metabolite resulted in obtaining a more potent derivative, which we designated as 2HP. Cytotoxicity studies indicated that 2HP is well-tolerated by human cells. Ongoing work is focusing on formulating the new compound into a nano-formulation to enhance its delivery. Also, to have a better idea about how this compound works, a proteomic approach is currently underway. Our findings suggest that 2HP is a potential new broad-spectrum antimicrobial agent. Further studies are needed to confirm these findings and to develop 2HP into a safe and effective treatment for MDR infections.

Keywords: broad-spectrum antimicrobials, carbapenem-resistant acinetobacter baumannii, drug discovery, methicillin-resistant staphylococcus aureus, multidrug-resistant, natural products

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