Numerical analysis and parametric optimization of surge protection devices in a long up-pumping water pipeline

Mubashir Ali Siddiqui,Hassan Ahmed,Muhammad Bilal Javed,Umair Shahid 대한기계학회 2019 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.33 No.1

This study aims to present a parametric analysis of combined use of two surge protection devices in a relatively very long up-pumping water supply pipeline. Transient conditions are induced by sudden pump tripping. The effects of four parameters of hydropneumatic tank, i.e., polytropic exponent, initial air volume, orifice diameter and wave celerity and two parameters of surge tank, i.e., tank volume and tank orifice diameter are investigated on pressure surges. The parameters are optimized to achieve reduced pressure fluctuations throughout the pipe length. A numerical model is developed to perform hydraulic transient analysis in the pipeline system. Governing partial differential equations for unsteady flows are solved by the method of characteristics (MOC) and are subsequently converted into algebraic form using finite difference method. To establish the authenticity of the model, it is experimentally validated by comparing the model results with the experimental results. The validated model is then employed to analyze the effects of various parameters of the two surge protection devices on pressure fluctuations along the pipe length. The results obtained from the study are optimized for safe operation and economic use of the system.

Exploration of synthetic multifunctional amides as new therapeutic agents for Alzheimer's disease through enzyme inhibition, chemoinformatic properties, molecular docking and dynamic simulation insights

Hassan, Mubashir,Abbasi, Muhammad Athar,Aziz-ur-Rehman, Muhammad Athar,Siddiqui, Sabahat Zahra,Hussain, Ghulam,Shah, Syed Adnan Ali,Shahid, Muhammad,Seo, Sung-Yum Elsevier 2018 Journal of theoretical biology Vol.458 No.-

<P><B>Abstract</B></P> <P>A new series of multifunctional amides has been synthesized having moderate enzyme inhibitory potentials and mild cytotoxicity. 2-Furyl(1-piperazinyl)methanone (<B>1</B>) was coupled with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (<B>2</B>) to form {4-[(3,5-dichloro-2-hydroxyphenyl)sulfonyl]-1-piperazinyl}(2-furyl)methanone (<B>3</B>). Different elecrophiles were synthesized by the reaction of various un/substituted anilines (<B>4a-o</B>) with 2-bromoacetylbromide (<B>5</B>), 2‑bromo‑<I>N</I>-(un/substituted-phenyl)acetamides (<B>6a-o</B>). Further, equimolar ratios of <B>3</B> and <B>6a-o</B> were allowed to react in the presence of K<SUB>2</SUB>CO<SUB>3</SUB> in acetonitrile to form desired multifunctional amides (<B>7a-o</B>). The structural confirmation of all the synthesized compounds was carried out by their EI-MS, IR, <SUP>1</SUP>H NMR and <SUP>13</SUP>C NMR spectral data. Enzyme inhibition activity was performed against acetyl and butyrylcholinestrase enzymes, whereby <B>7e</B> showed very good activity having IC<SUB>50</SUB> value of 5.54 ± 0.03 and 9.15 ± 0.01 <I>μ</I>M, respectively, relative to eserine, a reference standard. Hemolytic activity of the molecules was checked to asertain their cytotoxicity towards red blood cell membrance and it was observed that most of the compounds were not toxic up to certain range. Moreover, chemoinformatic protepties and docking simulation results also showed the significance of <B>7e</B> as compared to other compounds. Based on <I>in vitro</I> and <I>in silico</I> analysis <B>7e</B> could be used as a template for the development of new drugs against Alzheimer's disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Designing of multifunctional amides derivatives as acetyl and butyrylcholinesterase inhibitors. </LI> <LI> Chemoinformatic, molecular docking and simulation analysis was against most potent inhibitor <B>7e.</B> </LI> <LI> In vitro and in silico results showed the significance of <B>7e</B> and could be used as a template for novel drugs against Alzheimer's disease. </LI> </UL> </P>

Designing of promising medicinal scaffolds for Alzheimer’s disease through enzyme inhibition, lead optimization, molecular docking and dynamic simulation approaches

Hassan, Mubashir,Abbasi, Muhammad Athar,Aziz-ur-Rehman, Muhammad Athar,Siddiqui, Sabahat Zahra,Shahzadi, Saba,Raza, Hussain,Hussain, Ghulam,Shah, Syed Adnan Ali,Ashraf, Muhamamd,Shahid, Muhammad,Seo, Academic Press 2019 Bioorganic chemistry Vol.91 No.-

<P><B>Abstract</B></P> <P>In the designed research work, a series of 2-furoyl piperazine based sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer’s disease. The structures of the newly synthesized compounds were characterized through spectral analysis and their inhibitory potential was evaluated against butyrylcholinesterase (BChE). The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. Furthermore, compounds were inspected by Lipinki Rule and their binding profiles against BChE were discerned by molecular docking. The protein fluctuations in docking complexes were recognized by dynamic simulation. From our <I>in vitro</I> and <I>in silico</I> results <B>5c</B>, <B>5j</B> and <B>5k</B> were identified as promising lead compounds for the treatment of targeted disease.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Sulfonamide derivatives were synthesized as therapeutic agents to target the Alzheimer’s disease. </LI> <LI> The inhibitory potential of newly synthesized compounds were evaluated against butyrylcholinesterase (BChE). </LI> <LI> The cytotoxicity of these sulfonamides was also ascertained through hemolysis of bovine red blood cells. </LI> <LI> Computational analysis was performed to check their binding profile against target protein. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Numerical and experimental investigation of wind loadings on vertical axis wind turbine blade deflection

Muhammad Muzamil,Mubashir Ali Siddiqui,Jianjun Wu 대한기계학회 2016 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.30 No.12

This work focuses on experimental and numerical investigation of the deflection on VAWT blade surface against the high measured wind speeds that were simulated in FLUENT to obtain the corresponding static forces. The effect of forces, blade setting angle and thickness to chord ratio along with their combined effects on deflection were assessed experimentally and numerically. Three airfoils of gradually increasing thickness to chord ratio, NACA 0015, 0021 and 4412, were selected along with three levels of forces and tested at 5°, 10° and 15° of blade setting angle. A 3 3 factorial experimental design was used to perform experiments and Analysis of variance (ANOVA) confirmed that individual effects of force and thickness to chord ratio were the most significant factors while blade setting angle had lesser significance on deflected values. However, interactive effects of these parameters were significant. Minimum deflections were observed in the range of 0.25-0.28 mm on NACA 0021 at 3 kg force in combination with all blade setting angles. Maximum observed value of defection was 1 mm, which occurred at 9 kg force at 5°, 10° and 15° of blade setting angle on NACA 0015 and 4412 airfoil shapes. The results ensure that the blade structure remains stable at 9 kg which corresponds to 20 m/s wind speed without affecting the performance. The deflections obtained from Finite element method were compared with experimental results and found in good agreement with each other.

Solar feed water heating feasibility for a conventional steam power plant

Ahsan Alam,Mubashir Ali Siddiqui,Naveed ur Rehman 대한기계학회 2017 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.31 No.7

Technical and economic feasibility of heating feed water through parabolic trough solar collectors has been discussed in this paper. This integration of solar energy with steam plants saves extraction steam, thus increasing turbine output. The study is based on a 210 MW Heavy fuel oil (HFO) fired power plant for Karachi weather conditions. Pressurized hot water storage system is used as heat storage medium. TRNSYS software is used to find out useful energy collected through parabolic trough collectors and heat storage in pressurized hot water storage system. Life cycle savings (LCS) using HFO prices of two different periods i.e. May, 2014 (higher HFO price) and Feb., 2016 (lower HFO price) are calculated and compared. Effect of change in HFO price on LCS is also presented. Integration of higher pressure FWH with solar energy is found more feasible in terms of LCS as compared to lower pressure FWH. Same methodology can be deployed on other plants around the globe to determine LCS and economic feasibility.

2-Furoic piperazide derivatives as promising drug candidates of type 2 diabetes and Alzheimer’s diseases: <i>In vitro</i> and <i>in silico</i> studies

Abbasi, Muhammad Athar,Hassan, Mubashir,ur-Rehman, Aziz,Siddiqui, Sabahat Zahra,Hussain, Ghulam,Shah, Syed Adnan Ali,Ashraf, Muhammad,Shahid, Muhammad,Seo, Sung Yum Elsevier 2018 Computational biology and chemistry Vol.77 No.-

<P><B>Abstract</B></P> <P>The heterocyclic compounds have been extensively reported for their bioactivity potential. The current research work reports the synthesis of some new multi-functional derivatives of 2-furoic piperazide (<B>1</B>; 1-(2-furoyl)piperazine). The synthesis was initiated by reacting the starting compound <B>1</B> with 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (<B>2</B>) in a basic, polar and protic medium to obtain the parent sulfonamide <B>3</B> which was then treated with different electrophiles, <B>4a–g</B>, in a polar and aprotic medium to acquire the designed molecules, <B>5a</B>–<B>g</B>. These convergent derivatives were evaluated for their inhibitory potential against <I>α</I>-glucosidase, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Acarbose was used as a reference standard for <I>α</I>-glucosidase inhibition while eserine for AChE and BChE inhibition. Some of the synthesized compounds were identified as promising inhibitors of these three enzymes and their bioactivity potentials were also supported by molecular docking study. The most active compounds among the synthetic analogues might be helpful in drug discovery and development for the treatment of type 2 diabetes and Alzhiemer’s diseases.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthesis of multi-functional 2-furoic piperazide derivatives. </LI> <LI> Enzyme inhibitory studies against different enzymes. </LI> <LI> Computational studies to augment the <I>in vitro</I> results. </LI> <LI> Suitable therapeutic agents for type 2 diabetes and Alzheimer’s disease. </LI> <LI> Mild hemolytic agents toward red blood cell membrane. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthesis, <i>in vitro</i> and <i>in silico</i> studies of novel potent urease inhibitors: <i>N</i>-[4-({5-[(3-Un/substituted-anilino-3-oxopropyl)sulfanyl]-1,3,4-oxadiazol-2-yl}methyl)-1,3-thiazol-2-yl]benzamides

Abbasi, Muhammad Athar,Hassan, Mubashir,Aziz-ur-Rehman, Mubashir,Siddiqui, Sabahat Zahra,Raza, Hussain,Shah, Syed Adnan Ali,Seo, Sung-Yum Elsevier 2018 Bioorganic & medicinal chemistry Vol.26 No.13

<P><B>Abstract</B></P> <P>The present article describes the synthesis, <I>in vitro</I> urease inhibition and <I>in silico</I> molecular docking studies of a novel series of bi-heterocyclic bi-amides. The synthesis of title compounds was initiated by benzoylation, with benzoyl chloride (<B>1</B>), of the key starter ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (<B>2</B>) in weak basic aqueous medium followed by hydrazide formation, <B>4</B>, and cyclization with CS<SUB>2</SUB> to reach the parent bi-heterocyclic nucleophile, <I>N</I>-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-1,3-thiazol-2-yl}benzamide (<B>5</B>). Various electrophiles, <B>8a–l</B>, were synthesized by a two-step process and these were finally coupled with <B>5</B> to yield the targeted bi-heterocyclic bi-amide molecules, <B>9a–l</B>. The structures of the newly synthesized products were corroborated by IR, <SUP>1</SUP>H NMR, <SUP>13</SUP>C NMR, EI-MS and elemental analysis. The <I>in vitro</I> screening of these molecules against urease explored that most of the compounds exhibit potent inhibitory potential against this enzyme. The compound <B>9j</B>, with IC<SUB>50</SUB> value of 2.58 ± 0.02 µM, exhibited most promising inhibitory activity among the series, relative to standard thiourea having IC<SUB>50</SUB> value of 21.11 ± 0.12 µM. <I>In silico</I> studies fully augmented the experimental enzyme inhibition results. Chemo-informatics analysis showed that synthesized compounds (<B>9a–l</B>) mostly obeyed the Lipinski's rule. Molecular docking study suggested that ligand <B>9j</B> exhibited good binding energy value (−7.10 kcal/mol) and binds within the active region of target protein. So, on the basis of present investigation, it was inferred that <B>9j</B> may serve as a novel scaffold for designing more potent urease inhibitors.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthesis and structure-activity relationship of tyrosinase inhibiting novel bi-heterocyclic acetamides: Mechanistic insights through enzyme inhibition, kinetics and computational studies

Butt, Abdul Rehman Sadiq,Abbasi, Muhammad Athar,Aziz-ur-Rehman, Muhammad Athar,Siddiqui, Sabahat Zahra,Raza, Hussain,Hassan, Mubashir,Shah, Syed Adnan Ali,Shahid, Muhammad,Seo, Sung-Yum Elsevier 2019 Bioorganic chemistry Vol.86 No.-

<P><B>Abstract</B></P> <P>The present research was designed for the selective synthesis of novel bi-heterocyclic acetamides, <B>9a-n</B>, and their tyrosinase inhibition to overwhelm the problem of melanogenesis. The structures of newly synthesized compounds were confirmed by spectral techniques such as <SUP>1</SUP>H NMR, <SUP>13</SUP>C NMR, and EI-MS along with elemental analysis. The inhibitory effects of these bi-heterocyclic acetamides (<B>9a-n</B>) were evaluated against tyrosinase and all these molecules were recognized as potent inhibitors relative to the standard used. The Kinetics mechanism was analyzed by Lineweaver-Burk plots which explored that compound, <B>9h</B>, inhibited tyrosinase competitively by forming an enzyme-inhibitor complex. The inhibition constants K<I> <SUB>i</SUB> </I> calculated from Dixon plots for this compound was 0.0027 µM. The computational study was coherent with the experimental records and these ligands exhibited good binding energy values (kcal/mol). The hemolytic analysis revealed their mild cytotoxicity towards red blood cell membranes and hence, these molecules can be pondered as nontoxic medicinal scaffolds for skin pigmentation and related disorders.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthesis of novel bi-heterocyclic acetamides and their tyrosinase inhibition to overwhelm the problem of melanogenesis. </LI> <LI> <I>In vitro</I> and <I>in silico</I> analysis were performed to check their inhibitory potential against tyrosinase enzymes. </LI> <LI> The molecules with small sized methyl group/s at <I>ortho</I>-position/s in aryl part or a flexible phenethyl group, generally inhibited the tyrosinase in an excellent manner. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Synthesis of novel <i>N</i>-(1,3-thiazol-2-yl)benzamide clubbed oxadiazole scaffolds: Urease inhibition, Lipinski rule and molecular docking analyses

Athar Abbasi, Muhammad,Raza, Hussain,Aziz-ur-Rehman, Hussain,Zahra Siddiqui, Sabahat,Adnan Ali Shah, Syed,Hassan, Mubashir,Seo, Sung-Yum Elsevier 2019 Bioorganic chemistry Vol.83 No.-

<P><B>Abstract</B></P> <P>Present work aimed to synthesize some unique bi-heterocyclic benzamides as lead compounds for the <I>in vitro</I> inhibition of urease enzyme, followed by <I>in silico</I> studies. These targeted benzamides were synthesized in good yields through a multi-step protocol and their structures were confirmed by IR, <SUP>1</SUP>H NMR, <SUP>13</SUP>C NMR, EI-MS and elemental analysis. The <I>in vitro</I> screening results showed that most of the ligands exhibited good inhibitory potentials against the urease. Chemo-informatics analysis envisaged that all these compounds obeyed the Lipinski's rule. Molecular docking results showed that <B>7h</B> exhibited good binding energy value (−8.40 kcal/mol) and was bound within the active region of urease enzyme. From the present investigation, it was inferred that some of these potent urease inhibitors might serve as novel templates in drug designing.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Synthesis of bi-heterocyclic scaffolds. </LI> <LI> Structural characterization with spectral analysis. </LI> <LI> Urease inhibition and structure-activity relationship. </LI> <LI> Chemo-informatics and validation of Lipinski rule. </LI> <LI> Molecular docking analysis to ascertain interactions. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>