Investigation of non-hydroxamate scaffolds against HDAC6 inhibition: A pharmacophore modeling, molecular docking, and molecular dynamics simulation approach

Zeb, A.,Park, C.,Son, M.,Rampogu, S.,Alam, S. I.,Park, S. J.,Lee, K. W. Imperial College Press 2018 JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOG Vol.16 No.3

<P>Proteins deacetylation by Histone deacetylase 6 (HDAC6) has been shown in various human chronic diseases like neurodegenerative diseases and cancer, and hence is an important therapeutic target. Since, the existing inhibitors have hydroxamate group, and are not HDAC6-selective, therefore, this study has designed to investigate non-hydroxamate HDAC6 inhibitors. Ligand-based pharmacophore was generated from 26 training set compounds of HDAC6 inhibitors. The statistical parameters of pharmacophore (Hypo1) included lowest total cost of 115.63, highest cost difference of 135.00, lowest RMSD of 0.70 and the highest correlation of 0.98. The pharmacophore was validated by Fischer's Randomization and Test Set validation, and used as screening tool for chemical databases. The screened compounds were filtered by fit value (> 10.00), estimated Inhibitory Concentration (IC50) (<0.459), Lipinski's Rule of Five and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) Descriptors to identify drug-like compounds. Furthermore, the drug-like compounds were docked into the active site of HDAC6. The best docked compounds were selected having gold fitness score > 66.46 and chemscore < -28.31, and hydrogen bond interaction with catalytic active residues. Finally, three inhibitors having sulfamoyl group were selected by Molecular Dynamic (MD) simulation, which showed stable root mean square deviation (RMSD) (1.6-1.9 angstrom), lowest potential energy (< -6.3 x 10(5) kJ/mol), and hydrogen bonding with catalytic active residues of HDAC6.</P>

Effects of Oxidized Tallow on the Rabbit Serum Lipids and Antioxidant Activity of the In-vitro Lipids

Zeb, Alam,Rahman, Waheed Ur Korean Society of ToxicologyKorea Environmental Mu 2012 Toxicological Research Vol.28 No.3

This paper describes the effects of thermally oxidized tallow on the serum lipids profile and radical scavenging activity (RSA) of the lipids extracted from the different tissues of the rabbits. Tallow was thermally oxidized at $130^{\circ}C$ for 9, 18, 27, 36 and 45 h respectively. Thermally oxidized tallow was fed to the local strain of Himalayan rabbits for one week. Results show that oxidation increases the formation of hydroperoxides and decrease the level of radical scavenging activity of the tallow. The rabbit serum lipids profile showed a dose dependent increase in triglyceride, total cholesterol and LDL-cholesterol. However, no statistically significant increase was observed in the HDL-cholesterol with an increase of oxidation time. Serum glucose and rabbits body weight decrease significantly (p < 0.05) and was highly correlated with the serum lipids profile. The percent RSA of the lipids extracted from the liver, brain and muscles tissues showed a significant decrease with respect to 0.5, 1.0 and 1.5 g/body weight as well as oxidation time. Data suggests that thermal oxidation and use of thermally oxidized beef tallow is harmful and therefore an alternative way of cooking should be used.

Optimal Campaign Strategies in Fractional-Order Smoking Dynamics

Zeb, Anwar,Zaman, Gul,Jung, Il Hyo,Khan, Madad Verlag der Zeitschrift für Naturforschung 2014 Zeitschrift für Naturforschung. A, A journal Vol.69 No.5

<P>This paper deals with the optimal control problem in the giving up smoking model of fractional order. For the eradication of smoking in a community, we introduce three control variables in the form of education campaign, anti-smoking gum, and anti-nicotive drugs/medicine in the proposed fractional order model. We discuss the necessary conditions for the optimality of a general fractional optimal control problem whose fractional derivative is described in the Caputo sense. In order to do this, we minimize the number of potential and occasional smokers and maximize the number of ex-smokers. We use Pontryagin’s maximum principle to characterize the optimal levels of the three controls. The resulting optimality system is solved numerically by MATLAB.</P>

High payload itraconazole-incorporated lipid nanoparticles with modulated release property for oral and parenteral administration

Zeb, Alam,Qureshi, Omer S.,Kim, Hoo-Seong,Kim, Myung-Sic,Kang, Jong-Ho,Park, Jeong-Sook,Kim, Jin-Ki Wiley Blackwell (Blackwell Publishing) 2017 Journal of pharmacy and pharmacology Vol.69 No.8

Neuroprotective effects of carnosine-loaded elastic liposomes in cerebral ischemia rat model

Zeb Alam,Cha Ji-Hye,Noh Ah Reum,Qureshi Omer Salman,Kim Kyoung-Won,Choe Yeong-Hwan,Shin Donggeun,Shah Fawad Ali,Majid Arshad,Bae Ok-Nam,Kim Jin-Ki 한국약제학회 2020 Journal of Pharmaceutical Investigation Vol.50 No.4

Purpose The present study aims to investigate the neuroprotective effects of carnosine-entrapped elastic liposomes (CARELs) against cerebral ischemia. Methods CAR-ELs were prepared by extrusion method using egg phosphatidylcholine (eggPC) as a phospholipid and Tween 80 (TW80) as an edge activator (eggPC:TW80 = 8:2, w/w). The prepared CAR-ELs were purified by centrifugal ultrafiltration followed by characterization for particle size, polydispersity index, zeta potential and entrapment efficiency. The elasticity of CAR-ELs, the most distinct feature of elastic liposomes, was determined using a stainless steel pressure filter and compared with that of conventional liposomes. In vivo neuroprotective effects of CAR-ELs were evaluated in cerebral ischemia induced by permanent middle cerebral artery occlusion (pMCAO) in rats. CAR-ELs (250 mg/kg of CAR) were intravenously administered 20 min before pMCAO and 6 h after pMCAO, respectively. The infarct volume in brain was measured by staining with 2,3,5-triphenyltetrazolium chloride after 24 h of cerebral ischemia. Results CAR-ELs showed nanometric particle size near 100 nm and homogeneous distribution with polydispersity index below 0.1. The elasticity of CAR-ELs was 2-fold higher than that of conventional liposomes. The brain ischemia was successfully developed with pMCAO as indicated by highly infarcted hemisphere (~ 50%) in saline-treated rats. The pretreatment with CAR-ELs significantly reduced infarct volume (7.9%) compared with CAR solution (19.1%)- and saline (50.8%)-pretreated rats. CAR solution, however, showed better neuroprotective effects than CAR-ELs when administered 6 h after ischemia induction. Conclusion The pre-treatment with CAR-ELs could be promising nanocarrier-based neuroprotective therapeutics against ischemic stroke.

A new role of supercritical ethanol in macroalgae liquefaction (<i>Saccharina japonica</i>): Understanding ethanol participation, yield, and energy efficiency

Zeb, Hassan,Choi, Jaeyeon,Kim, Yunje,Kim, Jaehoon Elsevier 2017 ENERGY Vol.118 No.-

<P><B>Abstract</B></P> <P>Liquefaction of macroalgae was performed in a stirred autoclave reactor using supercritical ethanol (scEtOH) as a solvent. There was a sharp transition in ethanol consumption during macroalgae liquefaction in scEtOH when the temperature was increased from 350 to 400 °C. At 350 °C, a small amount of ethanol (6 wt%) reacted with intermediates, while at 400 °C, 18 wt% of the ethanol was consumed. Taking into account this increased consumption of ethanol at 400 °C, the bio-oil yield decreased from 79.2 to 53.9 wt%, energy recovery from 202.5% to 72.2%, and energy efficiency from 111.6% to 62.7%. The produced bio-oil had a molecular weight of 398 g mol<SUP>−1</SUP>, a HHV of 36.49 MJ kg<SUP>−1</SUP>, an O/C ratio of 0.12, and a H/C ratio of 1.58. To confirm the unique role of scEtOH in biomass liquefaction, subcritical water (subH<SUB>2</SUB>O) and supercritical water (scH<SUB>2</SUB>O)-based liquefactions were carried out and the results compared with those obtained for scEtOH-based liquefaction. GC-MS results from the bio-oil produced with scH<SUB>2</SUB>O revealed the percentage area of compounds containing an ethoxy group to be as low as 20%, while this value reached 62% when using scEtOH.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Supercritical ethanol not only acts as a solvent but also as a reagent. </LI> <LI> Ethanol consumption during reaction was calculated by GC-MS ethanol calibration. </LI> <LI> Bio-oil yield, ER and EE were re-calculated considering consumed amount of ethanol. </LI> <LI> Decrease in bio-oil yield, ER and EE when consumed ethanol was taken into account. </LI> </UL> </P>

Improved skin permeation of methotrexate via nanosized ultradeformable liposomes

Zeb, Alam,Qureshi, Omer Salman,Kim, Hyung-Seo,Cha, Ji-Hye,Kim, Hoo-Seong,Kim, Jin-Ki Dove Medical Press 2016 International journal of nanomedicine Vol.11 No.-

<P>The aim of this study is to investigate methotrexate-entrapped ultradeformable liposomes (MTX-UDLs) for potential transdermal application. MTX-UDLs were prepared by extrusion method with phosphatidylcholine as a bilayer matrix and sodium cholate or Tween 80 as an edge activator. The physicochemical properties of MTX-UDLs were determined in terms of particle size, polydispersity index, zeta potential, and entrapment efficiency. The deformability of MTX-UDLs was compared with that of methotrexate-entrapped conventional liposomes (MTX-CLs) using a steel pressure filter device. The skin permeation of MTX-UDLs was investigated using Franz diffusion cell, and the skin penetration depth of rhodamine 6G-entrapped UDLs was determined by confocal laser scanning microscopy. MTX-UDLs showed a narrow size distribution, with the particle size of ~100 nm. The deformability of MTX-UDLs was two to five times greater than that of MTX-CLs. The skin permeation of MTX-UDLs was significantly improved compared with MTX-CLs and free MTX solution. The optimized UDLs (phosphatidylcholine: Tween 80 =7:3, w/w) showed a higher fluorescence intensity than conventional liposomes at every increment of skin depth. Thus, the optimized UDLs could be promising nanocarriers for systemic delivery of MTX across skin.</P>

Effective conversion of the carbohydrate-rich macroalgae (<i>Saccharina japonica</i>) into bio-oil using low-temperature supercritical methanol

Zeb, Hassan,Riaz, Asim,Kim, Jaehoon Elsevier 2017 Energy conversion and management Vol.151 No.-

<P><B>Abstract</B></P> <P>The use of supercritical methanol (scMeOH) for the liquefaction of the carbohydrate-rich macroalgae <I>Saccharina japonica</I> was investigated at low temperature (250–300°C). At 300°C, almost complete conversion (98.1wt%) and a high bio-oil yield (66.0wt%) were achieved. These values are higher than those achieved with supercritical ethanol (scEtOH, 87.8wt% conversion, 60.5wt% bio-oil yield) and subcritical water (subH<SUB>2</SUB>O, 91.9wt% conversion, 40.3wt% bio-oil yield) under identical reaction conditions. The superior liquefaction in scMeOH is attributed to the beneficial physical properties of scMeOH, including its higher polarity, superior reactivity, and higher acidity. The superior reactivity of scMeOH was evident from the larger amount of esters (54.6 area%) produced in scMeOH as compared to that in scEtOH (47.2 area%), and the larger amount of methyl/methoxy-containing compounds (78.6 area%) produced in scMeOH than that of ethyl/ethoxy-containing compounds (58.2 area%) produced in scEtOH. The higher bio-oil yield combined with its higher calorific value (29.2MJkg<SUP>−1</SUP>) resulted in a higher energy recovery of 135% for scMeOH as compared to those of scEtOH (118%) and subH<SUB>2</SUB>O (96%). When considering the amount of alcohol consumed during the liquefactions and the production of light bio-oil fractions that evaporate during bio-oil recovery, the higher methanol consumption (5.3wt%) than that of ethanol (2.3wt%) leads to similar bio-oil yields (∼51wt%).</P> <P><B>Highlights</B></P> <P> <UL> <LI> 98.1% carbohydrate-rich macroalgae was converted in scMeOH at 300°C. </LI> <LI> The conversion in scMeOH was higher than those of scEtOH (87.8%) and subH<SUB>2</SUB>O (91.9%). </LI> <LI> Higher energy recovery values of scMeOH than those of scEtOH and subH<SUB>2</SUB>O. </LI> <LI> High reactivity of scMeOH can be the reason for high conversion. </LI> <LI> Higher consumption of methanol than ethanol verified the high reactivity of scMeOH. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

High-yield bio-oil production from macroalgae (<i>Saccharina japonica</i>) in supercritical ethanol and its combustion behavior

Zeb, Hassan,Park, Jongkeun,Riaz, Asim,Ryu, Changkook,Kim, Jaehoon Elsevier 2017 CHEMICAL ENGINEERING JOURNAL -LAUSANNE- Vol.327 No.-

<P><B>Abstract</B></P> <P>The effect of reaction parameters (temperature, time and biomass-to-solvent (BS) ratio) on properties (higher heating value (HHV) and O/C and H/C ratios) and yields of bio-oil produced from macroalgae (<I>Saccharina japonica</I>) liquefaction using supercritical ethanol (scEtOH) as a solvent was investigated. At 400°C using a BS ratio of 1/10 and reaction time of 45min, a high yield of bio-oil (88wt%) with a HHV of 35.0MJkg<SUP>−1</SUP>, O/C ratio of 0.14, and H/C ratio of 1.62 was obtained. Compared with water-based liquefaction, (subcritical water at 300°C, bio-oil yield of 43wt%, HHV of 20.7MJkg<SUP>−1</SUP>, O/C ratio of 0.48, and H/C ratio of 2.01; supercritical water at 400°C, bio-oil yield of 37wt%, HHV of 29.0MJkg<SUP>−1</SUP>, O/C ratio of 0.18, and H/C ratio of 1.76), the yield and energy content of the bio-oil produced using scEtOH were significantly higher. This enhancement was attributed to the reactivity of scEtOH with the intermediates generated from macroalgae. The utility of the generated bio-oil was demonstrated by application in a commercial 100 MW<SUB>e</SUB> generation plant. The thermal efficiency of the bio-oil (86.0%) was quite similar to that of heavy fuel oil (HFO) (87.1%), suggesting that the HFO could be fully replaced by the bio-oil.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Almost complete conversion of macroalgae in supercritical ethanol (scEtOH). </LI> <LI> High-yield (88wt%) and high-energy-content (35MJkg<SUP>−1</SUP>) bio-oil produced in scEtOH. </LI> <LI> ScEtOH produced higher-yield and better-quality bio-oil than water-based reaction. </LI> <LI> Bio-oil can be used as a combustion fuel for green electricity generation. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

A comprehensive review on inverter topologies and control strategies for grid connected photovoltaic system

Zeb, Kamran,Uddin, Waqar,Khan, Muhammad Adil,Ali, Zunaib,Ali, Muhammad Umair,Christofides, Nicholas,Kim, H.J. Elsevier 2018 RENEWABLE & SUSTAINABLE ENERGY REVIEWS Vol.94 No.-

<P><B>Abstract</B></P> <P>The application of Photovoltaic (PV) in the distributed generation system is acquiring more consideration with the developments in power electronics technology and global environmental concerns. Solar PV is playing a key role in consuming the solar energy for the generation of electric power. The use of solar PV is growing exponentially due to its clean, pollution-free, abundant, and inexhaustible nature. In grid-connected PV systems, significant attention is required in the design and operation of the inverter to achieve high efficiency for diverse power structures. The requirements for the grid-connected inverter include; low total harmonic distortion of the currents injected into the grid, maximum power point tracking, high efficiency, and controlled power injected into the grid. The performance of the inverters connected to the grid depends mainly on the control scheme applied. In this review, the global status of the PV market, classification of the PV system, configurations of the grid-connected PV inverter, classification of various inverter types, and topologies are discussed, described and presented in a schematic manner. A concise summary of the control methods for single- and three-phase inverters has also been presented. In addition, various controllers applied to grid-tied inverter are thoroughly reviewed and compared. Finally, the criteria for the selection of inverters and the future trends are comprehensively presented.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The global PV market and classification of PV systems. </LI> <LI> Various inverter topologies presented in a schematic manner. </LI> <LI> Review of the control techniques for single- and three-phase inverters. </LI> <LI> Selection guide for choosing an appropriate inverter topology based on specific application. </LI> </UL> </P>