Publications by authors named "Syed Badshah"

41 Publications

Isolation, Characterization, and Medicinal Potential of Polysaccharides of .

Molecules 2021 Mar 8;26(5). Epub 2021 Mar 8.

Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Mushroom polysaccharides are active medicinal compounds that possess immune-modulatory and anticancer properties. Currently, the mushroom polysaccharides krestin, lentinan, and polysaccharopeptides are used as anticancer drugs. They are an unexplored source of natural products with huge potential in both the medicinal and nutraceutical industries. The northern parts of Pakistan have a rich biodiversity of mushrooms that grow during different seasons of the year. Here we selected an edible (true morels) of the Ascomycota group for polysaccharide isolation and characterization. Polysaccharopeptides and polysaccharides from this mushroom were isolated using the green chemistry, hot water treatment method. Fourier transform infrared spectroscopy revealed the sugar nature and possible beta-glucan type structure of these polysaccharides. Antioxidant assays showed that the deproteinized polysaccharides have moderate free radical scavenging activity. These isolated polysaccharides exhibited good acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) inhibition activities. Therefore, these polysaccharides may be valuable for the treatment of Alzheimer's and Parkinson's diseases. Further bioassays are needed to discover the true potential of polysaccharides for medicinal purposes.
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http://dx.doi.org/10.3390/molecules26051459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962536PMC
March 2021

Identification of Potential HCV Inhibitors Based on the Interaction of Epigallocatechin-3-Gallate with Viral Envelope Proteins.

Molecules 2021 Feb 26;26(5). Epub 2021 Feb 26.

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.

Hepatitis C is affecting millions of people around the globe annually, which leads to death in very high numbers. After many years of research, hepatitis C virus (HCV) remains a serious threat to the human population and needs proper management. The in silico approach in the drug discovery process is an efficient method in identifying inhibitors for various diseases. In our study, the interaction between Epigallocatechin-3-gallate, a component of green tea, and envelope glycoprotein E2 of HCV is evaluated. Epigallocatechin-3-gallate is the most promising polyphenol approved through cell culture analysis that can inhibit the entry of HCV. Therefore, various in silico techniques have been employed to find out other potential inhibitors that can behave as EGCG. Thus, the homology modelling of E2 protein was performed. The potential lead molecules were predicted using ligand-based as well as structure-based virtual screening methods. The compounds obtained were then screened through PyRx. The drugs obtained were ranked based on their binding affinities. Furthermore, the docking of the topmost drugs was performed by AutoDock Vina, while its 2D interactions were plotted in LigPlot+. The lead compound mms02387687 (2-[[5-[(4-ethylphenoxy) methyl]-4-prop-2-enyl-1,2,4-triazol-3-yl] sulfanyl]-N-[3(trifluoromethyl) phenyl] acetamide) was ranked on top, and we believe it can serve as a drug against HCV in the future, owing to experimental validation.
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http://dx.doi.org/10.3390/molecules26051257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956288PMC
February 2021

Synthesis of PEG-4000-co-poly (AMPS) nanogels by cross-linking polymerization as highly responsive networks for enhancement in meloxicam solubility.

Drug Dev Ind Pharm 2021 Mar 2;47(3):465-476. Epub 2021 Mar 2.

School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system.
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http://dx.doi.org/10.1080/03639045.2021.1892738DOI Listing
March 2021

Identification of potential inhibitors of Zika virus NS5 RNA-dependent RNA polymerase through virtual screening and molecular dynamic simulations.

Saudi Pharm J 2020 Dec 21;28(12):1580-1591. Epub 2020 Oct 21.

Department of Chemical Engineering, College of Engineering, King Saud University, Riyadh, Saudi Arabia.

Zika virus (ZIKV) is one of the mosquito borne flavivirus with several outbreaks in past few years in tropical and subtropical regions. The non-structural proteins of are suitable active targets for inhibitory drugs due to their role in pathogenicity. In ZIKV, the non-structural protein 5 (NS5) RNA-Dependent RNA polymerase replicates its genome. Here we have performed virtual screening to identify suitable ligands that can potentially halt the ZIKV NS5 RNA dependent RNA polymerase (RdRp). During this process, we searched and screened a library of ligands against ZIKV NS5 RdRp. The selected ligands with significant binding energy and ligand-receptor interactions were further processed. Among the selected docked conformations, top five was further optimized at atomic level using molecular dynamic simulations followed by binding free energy calculations. The interactions of ligands with the target structure of ZIKV RdRp revealed that they form strong bonds within the active sites of the receptor molecule. The efficacy of these drugs against ZIKV can be further analyzed through and studies.
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http://dx.doi.org/10.1016/j.jsps.2020.10.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783101PMC
December 2020

Porous and highly responsive cross-linked β-cyclodextrin based nanomatrices for improvement in drug dissolution and absorption.

Life Sci 2021 Feb 30;267:118931. Epub 2020 Dec 30.

Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, China.

Aims: Aim of the study was to enhance the solubility of Chlorthalidone by developing beta-cyclodextrin cross-linked hydrophilic nanomatrices.

Main Methods: Nine different formulations were fabricated by free radical polymerization technique. All formulations were characterized through different studies. FTIR spectroscopy of unloaded and loaded nanomatrices was processed to determine compatibility of constituents and that of the drug with the system. Surface morphology of the nanomatrices was studied by SEM. The size of the optimized formulation was determined by zeta sizer. Swelling, in-vitro release and solubility studies were carried out in different media and results of in-vitro release profiles of nanomatrices and commercially available tablet of Chlorthalidone were compared. For determination of biocompatibility, toxicity studies were proclaimed in rabbits.

Key Findings: Main peaks of corresponding functional groups of individual constituents and that of drug were depicted in FTIR spectra of unloaded and loaded nanomatrices. Porous and fluffy structure was visualized through SEM images. Particle size of the optimized formulation was in the range of 175 ± 5.27 nm. Percent loading of optimized formulation showed the best result. Comparing the in-vitro drug release profiles of nanomatrices and commercially available tablet, the results of the synthesized nanomatrices were quite satisfactory. Solubility profiles were also high as compared to the drug alone. Moreover, toxicity studies confirmed that nanomatrices were biocompatible and no sign of any toxic effect was found.

Significance: We concluded that our developed nanomatrices had successfully enhanced the solubility of Chlorthalidone and can also be used for other poorly aqueous soluble drugs.
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http://dx.doi.org/10.1016/j.lfs.2020.118931DOI Listing
February 2021

Important Flavonoids and Their Role as a Therapeutic Agent.

Molecules 2020 Nov 11;25(22). Epub 2020 Nov 11.

Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.

Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry. Flavonoids possess a number of medicinal benefits, including anticancer, antioxidant, anti-inflammatory, and antiviral properties. They also have neuroprotective and cardio-protective effects. These biological activities depend upon the type of flavonoid, its (possible) mode of action, and its bioavailability. These cost-effective medicinal components have significant biological activities, and their effectiveness has been proved for a variety of diseases. The most recent work is focused on their isolation, synthesis of their analogs, and their effects on human health using a variety of techniques and animal models. Thousands of flavonoids have been successfully isolated, and this number increases steadily. We have therefore made an effort to summarize the isolated flavonoids with useful activities in order to gain a better understanding of their effects on human health.
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http://dx.doi.org/10.3390/molecules25225243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697716PMC
November 2020

Spread of coronavirus disease-19 among devotees during religious congregations.

Ann Thorac Med 2020 Jul-Sep;15(3):105-106. Epub 2020 Jun 18.

Department of Chemistry and Biochemistry, Islamia College University, Peshawar, Pakistan.

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http://dx.doi.org/10.4103/atm.ATM_162_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423201PMC
June 2020

Eu , Sm Deep-Red Phosphors as Novel Materials for White Light-Emitting Diodes and Simultaneous Performance Enhancement of Organic-Inorganic Perovskite Solar Cells.

Small 2020 Jun 27;16(25):e2001551. Epub 2020 May 27.

Department of Chemistry, King Fahd University of Petroleum & Minerals, Dhahran, 31261, Saudi Arabia.

The luminous efficiency of inorganic white light-emitting diodes, to be used by the next generation as light initiators, is continuously progressing and is an emerging interest for researchers. However, low color-rendering index (Ra), high correlated color temperature (CCT), and poor stability limit its wider application. Herein, it is reported that Sm - and Eu -doped calcium scandate (CaSc O (CSO)) are an emerging deep-red-emitting material with promising light absorption, enhanced emission properties, and excellent thermal stability that make it a promising candidate with potential applications in emission display, solid-state white lighting, and the device performance of perovskite solar cells (PSCs). The average crystal structures of Sm -doped CSO are studied by synchrotron X-ray data that correspond to an extremely rigid host structure. Samarium ion is incorporated as a sensitizer that enhances the emission intensity up to 30%, with a high color purity of 88.9% with a 6% increment. The impacts of hosting the sensitizer are studied by quantifying the lifetime curves. The CaSc O :0.15Eu ,0.03Sm phosphor offers significant resistance to thermal quenching. The incorporation of lanthanide ion-doped phosphors CSOE into PSCs is investigated along with their potential applications. The CSOE-coated PSCs devices exhibit a high current density and a high power conversion efficiency (15.96%) when compared to the uncoated control devices.
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http://dx.doi.org/10.1002/smll.202001551DOI Listing
June 2020

Structural insights into the Zika virus NS1 protein inhibition using a computational approach.

J Biomol Struct Dyn 2021 May 6;39(8):3004-3011. Epub 2020 May 6.

Department of Chemistry, Islamia College University, Peshawar, Pakistan.

Zika virus is part of the flaviviruses that spread through the Aedes mosquito species and causes neurological infectious diseases. The non-structural protein 1 (NS1) is an essential enzyme that is involved in the replication of Zika virus. In this study, the newly isolated flavonoid analogs were docked against the NS1 protein. Most of the compounds showed strong interactions with favorable binding energies in the active site of NS1. One of the suitable docked ligand-protein complexes was simulated along with the apo form of the enzyme for 100 ns. The simulation results validated the docking data. The molecular dynamics simulation analysis comprising of root mean square deviation and fluctuation, the radius of gyration, hydrogen bonding, potential energy, principle component analysis, and MM/PBSA revealed about the stability of the apo and complex systems. These flavonoids analogs can inhibit the hexamerization of the NS1 which is necessary for the Zika virus replication.Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1759453DOI Listing
May 2021

Spread of Novel coronavirus by returning pilgrims from Iran to Pakistan.

J Travel Med 2020 05;27(3)

Department of Molecular Biology and Genetics, Institute of Basic Medical Sciences, Khyber Medical University, F1 Phase-6 Rd, Phase-6 Hayatabad, 25100, Peshawar, Pakistan.

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http://dx.doi.org/10.1093/jtm/taaa044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184355PMC
May 2020

Characterization and deployment of surface-engineered chitosan-triethylenetetramine nanocomposite hybrid nano-adsorbent for divalent cations decontamination.

Int J Biol Macromol 2020 Jun 20;152:663-671. Epub 2020 Feb 20.

Tecnologico de Monterrey, School of Engineering and Sciences, Campus Monterrey, Ave. Eugenio Garza Sada 2501, CP 64849 Monterrey, N.L., Mexico.

The latency of toxic cations in the ecosystem poses serious ecological problems due to its bioaccumulation potential and toxicity to living organisms. The effective removal of these wastewater cations releasing from multi-industries is a bottleneck issue. Therefore, an attempt has been made to design a suitable sorbent for cations sorption from the aqueous environment. The chitosan biopolymer was modified with triethylenetetramine to incorporate active sites in the polymeric sequence to boost up its cations sorption capacity. Triethylenetetramine molecule anchoring chitosan (CH-TET) was authenticated through elemental assay, Fourier-transform infrared spectroscopy and C NMR in solid-state, scanning electron microscopy and thermal analysis. The sorption of lead (1.94 mmol g), copper (2.79 mmol g) and nickel (1.53 mmol g) was carried out using the functionalized chitosan from aqueous solution, which showed higher sorption capacity for lead and copper than the pristine chitosan in terms of Langmuir sorption isotherm. To scrutinize the mechanism of sorption and energy of interaction between sorbent and sorbate, Langmuir, Temkin, and Freundlich isotherm models were used for sorption study. The Langmuir model showed the best fitting to the results based on lower error function values and a higher correlation coefficient (R). It can be concluded that the triethylenetetramine-modified chitosan might be considered as an effective sorbent for cations removal from industrial wastewater.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.02.218DOI Listing
June 2020

Chitosan-Based Bio-Composite Modified with Thiocarbamate Moiety for Decontamination of Cations from the Aqueous Media.

Molecules 2020 Jan 6;25(1). Epub 2020 Jan 6.

Tecnologico de Monterrey, School of Engineering and Sciences, Campus Monterrey, Ave. Eugenio Garza Sada 2501, Monterrey CP 64849, Mexico.

Herein, we report the development of chitosan (CH)-based bio-composite modified with acrylonitrile (AN) in the presence of carbon disulfide. The current work aimed to increase the Lewis basic centers on the polymeric backbone using single-step three-components (chitosan, carbon disulfide, and acrylonitrile) reaction. For a said purpose, the thiocarbamate moiety was attached to the pendant functional amine (NH) of chitosan. Both the pristine CH and modified CH-AN bio-composites were first characterized using numerous analytical and imaging techniques, including C-NMR (solid-form), Fourier-transform infrared spectroscopy (FTIR), elemental investigation, thermogravimetric analysis, and scanning electron microscopy (SEM). Finally, the modified bio-composite (CH-AN) was deployed for the decontamination of cations from the aqueous media. The sorption ability of the CH-AN bio-composite was evaluated by applying it to lead and copper-containing aqueous solution. The chitosan-based CH-AN bio-composite exhibited greater sorption capacity for lead (2.54 mmol g) and copper (2.02 mmol g) than precursor chitosan from aqueous solution based on Langmuir sorption isotherm. The experimental findings fitted better to Langmuir model than Temkin and Freundlich isotherms using linear regression method. Different linearization of Langmuir model showed different error functions and isothermal parameters. The nonlinear regression analysis showed lower values of error functions as compared with linear regression analysis. The chitosan with thiocarbamate group is an outstanding material for the decontamination of toxic elements from the aqueous environment.
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http://dx.doi.org/10.3390/molecules25010226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982774PMC
January 2020

Nanogels as drug-delivery systems: a comprehensive overview.

Ther Deliv 2019 11 2;10(11):697-717. Epub 2019 Dec 2.

Department of Pharmacy, Faculty of Pharmacy & Alternative Medicine, The Islamia University of Bahawalpur, 63100, Punjab, Pakistan.

Nanogels have attracted considerable attention as nanoscopic drug carriers, particularly for site-specific or time-controlled delivery of bioactive mediators. A high diversity of polymer systems and the simple modification of their physicochemical features have provided multipurpose forms of nanogel preparations. Nanogels have outstandingly high stability, drug loading ability, biologic consistence, good permeation capability and can be responsive to environmental stimuli. Great potential has been shown by nanogels in many fields including delivery of genes, chemotherapy drugs, diagnosis, targeting of specific organs and several others. This review focuses mainly on different types of nanogels, methods of preparation including methods of drug loading, different modes of biodegradation mechanisms as well as main mechanisms of drug release from nanogels. Recent applications of nanogels are also briefly discussed and exemplified.
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http://dx.doi.org/10.4155/tde-2019-0010DOI Listing
November 2019

Photosystem II oxygen-evolving complex photoassembly displays an inverse H/D solvent isotope effect under chloride-limiting conditions.

Proc Natl Acad Sci U S A 2019 09 4;116(38):18917-18922. Epub 2019 Sep 4.

Department of Chemistry, The Graduate Center of the City University of New York, New York, NY 10016.

Photosystem II (PSII) performs the solar-driven oxidation of water used to fuel oxygenic photosynthesis. The active site of water oxidation is the oxygen-evolving complex (OEC), a MnCaO cluster. PSII requires degradation of key subunits and reassembly of the OEC as frequently as every 20 to 40 min. The metals for the OEC are assembled within the PSII protein environment via a series of binding events and photochemically induced oxidation events, but the full mechanism is unknown. A role of proton release in this mechanism is suggested here by the observation that the yield of in vitro OEC photoassembly is higher in deuterated water, DO, compared with HO when chloride is limiting. In kinetic studies, OEC photoassembly shows a significant lag phase in HO at limiting chloride concentrations with an apparent H/D solvent isotope effect of 0.14 ± 0.05. The growth phase of OEC photoassembly shows an H/D solvent isotope effect of 1.5 ± 0.2. We analyzed the protonation states of the OEC protein environment using classical Multiconformer Continuum Electrostatics. Combining experiments and simulations leads to a model in which protons are lost from amino acid that will serve as OEC ligands as metals are bound. Chloride and DO increase the proton affinities of key amino acid residues. These residues tune the binding affinity of Mn and facilitate the deprotonation of water to form a proposed μ-hydroxo bridged MnMn intermediate.
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http://dx.doi.org/10.1073/pnas.1910231116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754581PMC
September 2019

Molecular docking and simulation of Zika virus NS3 helicase.

BMC Chem 2019 Dec 17;13(1):67. Epub 2019 May 17.

4Department of Pharmaceutical Chemistry, College of Pharamacy, King Khalid University, Abha, 61441 Saudi Arabia.

The Zika virus (ZIKV) has gained attention for the last few years due to the congenital microcephaly and Guillain-Barre Syndrome that resulted in humans. The non-structural protein-3 (NS3) helicase of ZIKV play an important role in viral RNA replication. In this article, we performed hundred nanosecond molecular dynamics simulation and molecular docking of the NS3 helicase of ZIKV with 1,4-benzothiazine derivatives. The root mean square deviation (RMSD) analyses showed the stability of the NS3 helicase. The simulation showed that the flexible and rigid domains of the protein play a crucial role during the RNA replication process. All such domains with ligand binding pockets can be targeted for drug design. The molecular docking showed that the strong hydrogen bonding and arene-cation interactions are responsible for the binding between NS3 and 1,4-benzothiazine derivatives, which provides a new dimension for potent drug design for ZIKV.
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http://dx.doi.org/10.1186/s13065-019-0582-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661806PMC
December 2019

Computational studies of 2-(4-oxo-3-phenylthiazolidin-2-ylidene)malononitrile.

BMC Chem 2019 Dec 18;13(1):25. Epub 2019 Feb 18.

7Department of Chemistry, Islamia College University Peshawar, Peshawar, 25120 KPK Pakistan.

The molecular structure of the 2-(4-oxo-3-phenylthiazolidin-2-ylidene) malononitrile () is calculated using DFT B3LYP/6-311G(d, p) method. The calculated geometric parameters are in good agreement with the experimental data. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and study the different intramolecular charge transfer (ICT) interactions occurring in the studied system. The BD(2)C17-C19 → BD*(2)C14-C15, LP(2)O2 → BD*(1)N5-C9 and LP(1)N5 → BD*(2)C10-C11 ICT interactions causing stabilization of the system by 23.30, 30.63 and 52.48 kcal/mol, respectively. The two intense electronic transition bands observed experimentally at 249 nm and 296 nm are predicted using the TD-DFT calculations at 237.9 nm (f = 0.1618) and 276.4 nm (f = 0.3408), respectively. These electronic transitions are due to H-3 → L (94%) and H → L (95%) excitations, respectively.
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http://dx.doi.org/10.1186/s13065-019-0542-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661733PMC
December 2019

Nonenzymatic amperometric dopamine sensor based on a carbon ceramic electrode of type SiO/C modified with CoO nanoparticles.

Mikrochim Acta 2019 06 25;186(7):471. Epub 2019 Jun 25.

Interdisciplinary Research Centre in Biomedical Materials (IRCBM), COMSATS University Islamabad, Lahore Campus, Defence Road, Off Raiwind Road, Lahore, 54000, Pakistan.

An amperometric nonenzymatic dopamine sensor has been developed. Cobalt oxide (CoO) nanoparticles were uniformly dispersed inside mesoporous SiO/C. A sol-gel process was used for the preparation of this mesoporous composite material (SiO/C). This mesoporous composite has a pore size of around 13-14 nm, a large surface area (S 421 m·g) and large pore volume (0.98 cm·g) as determined by the BET technique. The material compactness was confirmed by SEM images which showing that there is no phase segregation at the magnification applied. The chemical homogeneity of the materials was confirmed by EDX mapping. The SiO/C/CoO nanomaterial was pressed in desk format to fabricate a working electrode for nonenzymatic amperometric sensing of dopamine at a pH value of 7.0 and at a typical working potential of 0.25 V vs SCE. The detection limit, linear response range and sensitivity are 0.018 μmol L, 10-240 μmol L, and 80 μA·μmol L cm, respectively. The response timé of the electrode is less than 1 s in the presence of 60 μmol L of dopamine. The sensor showed chemically stability, high sensitivity and is not interfered by other electroactive molecules present in blood. The repeatability of this sensor was evaluated as 1.9% (RSD; for n = 10 at a 40 μmol Ldopamine level. Graphical abstract Schematic presentation of the preparation of a nanostructured composite of type SiO/C/CoO for electrooxidative sensing of dopamine.
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http://dx.doi.org/10.1007/s00604-019-3605-4DOI Listing
June 2019

pH/Thermo-Dual Responsive Tunable In Situ Cross-Linkable Depot Injectable Hydrogels Based on Poly(N-Isopropylacrylamide)/Carboxymethyl Chitosan with Potential of Controlled Localized and Systemic Drug Delivery.

AAPS PharmSciTech 2019 Feb 21;20(3):119. Epub 2019 Feb 21.

Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, Punjab, 63100, Pakistan.

In the current study, cytocompatible in situ cross-linkable pH/thermo-dual responsive injectable hydrogels were prepared based on poly(N-isopropylacrylamide) and carboxymethyl chitosan, i.e., poly(CMCS-g-NIPAAm). The prepared formulations were aimed to be used as drug depot of 5-fluorouracil (5-FU) after subcutaneous administration in vivo. The phase transition from sol-gel state under physiologic temperature range was analyzed and confirmed by tube titling and optical transmittance measurements. The viscoelastic properties of gel formulations were confirmed by rheology determination via time sweep, temperature, and continuous ramp test. Oscillatory swelling cycles confirmed temperature effect and structural changes. pH and temperature sensitivity of dual responsive gels were analyzed at different pH and temperature programs. In vitro drug release profile displayed that developed formulations have the highest release in acidic pH at 25°C. The safety of blank gel formulations was evaluated against L929 cell lines via MTT assay and confirmed cytocompatibility with no detectable toxicity. In vitro cytotoxic potential of drug-loaded gels against HeLa and MCF-7 cancer cell lines confirmed that 5-FU has controlled cytotoxic potential in depot form in comparison to free 5-FU solution. The IC values for free 5-FU (21 ± 05 μg/ml and 18 ± 66 μg/ml) were found higher in comparison to the loaded form. The copolymer structure formation was confirmed by NMR and FTIR spectroscopic analysis. TG and DSC analysis proved the thermal stability and phase transition temperatures of pure and copolymer samples, while SEM analysis showed the porous nature of in situ formed hydrogels. It was concluded from the results that the developed formulations have pH/temperature sensitivity with potential of systemic and intratumoral controlled drug delivery properties.
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http://dx.doi.org/10.1208/s12249-019-1328-9DOI Listing
February 2019

Bioactivity Profile of the Diterpene Isosteviol and its Derivatives.

Molecules 2019 Feb 14;24(4). Epub 2019 Feb 14.

Department of Chemistry, Islamia College University Peshawar, Peshawar 25120, Pakistan.

Steviosides, rebaudiosides and their analogues constitute a major class of naturally occurring biologically active diterpene compounds. The wide spectrum of pharmacological activity of this group of compounds has developed an interest among medicinal chemists to synthesize, purify, and analyze more selective and potent isosteviol derivatives. It has potential biological applications and improves the field of medicinal chemistry by designing novel drugs with the ability to cope against resistance developing diseases. The outstanding advancement in the design and synthesis of isosteviol and its derivative has proved its effectiveness and importance in the field of medicinal chemical research. The present review is an effort to integrate recently developed novel drugs syntheses from isosteviol and potentially active pharmacological importance of the isosteviol derivatives covering the recent advances.
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http://dx.doi.org/10.3390/molecules24040678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412665PMC
February 2019

Preparation and Evaluation of Skin Wound Healing Chitosan-Based Hydrogel Membranes.

AAPS PharmSciTech 2018 Oct 31;19(7):3199-3209. Epub 2018 Aug 31.

Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, Punjab, 63100, Pakistan.

The purpose of the study was to synthesize and characterize a new form of topical membranes as chitosan-based hydrogel membranes for bacterial skin infections. The polymeric membranes were synthesized by modification in free radical solution polymerization technique. High molecular weight (HMW) chitosan polymer was cross-linked with monomer 2-acrylamido-2-methylpropane sulfonic acid (AMPS) through cross-linker N,N-methylenebisacrylamide (MBA). Mupirocin, an antibiotic, was used as model drug. The polymeric membranes were prepared in spherical form that found stable and elastic. Characterization of hydrogel membranes was performed by FTIR, SEM, DSC, TGA, swelling behavior, drug release, irritation study, and ex vivo drug permeation and deposition study. Structural and thermal studies confirmed the formation of new polymeric network with enhanced stability of hydrogel membranes. Permeation flux of drug from optimized formulation through rabbit's skin assessed by using Franz cell was up to 104.09 μg cm h. Furthermore, hydrogel membrane has significant retention of drug in skin up to 2185 μg 1.5 cm. Draize patch test confirmed the synthesized hydrogels as non-irritant to skin. The preparation of a topical membrane with improved antibacterial activity within controlled release manner is desirable for the advancement and treatment of skin diseases.
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http://dx.doi.org/10.1208/s12249-018-1131-zDOI Listing
October 2018

New developments in non-quinolone-based antibiotics for the inhibiton of bacterial gyrase and topoisomerase IV.

Eur J Med Chem 2018 May 1;152:393-400. Epub 2018 May 1.

Department of Chemistry, Islamia College University, Peshawar 25120, Pakistan.

The inhibition of pathogenic bacteria at the replication stage is important to halt their further reproduction and spread. The replication enzymes include the DNA gyrase and topoisomerase IV that are recognized targets for the infection control. Novel antibiotic compounds are always in demand for targeting different active sites of these enzymes. Although quinolones are the current drug of choice for targeting these enzymes, emerging resistance is a global concern. Wide-scale efforts are needed to overcome the emerging resistance by designing more potent drugs. In this article, we have reviewed the last five years progress of various classes of non-quinolone-based chemical compounds that are tested for their antibacterial activities.
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http://dx.doi.org/10.1016/j.ejmech.2018.04.059DOI Listing
May 2018

Better agonist for the opioid receptors.

Chem Cent J 2018 Feb 8;12(1):13. Epub 2018 Feb 8.

Department of Chemistry, College of Sciences, King Saud University, Riyadh, Saudi Arabia.

This commentary highlights the recent work published in journal Nature on the structural based discovery of novel analgesic compounds for opioid receptors with minimal effects. Manglik et al. selectively targeted the Gi based μOR pathway instead of the β-arrestin pathway of the opioids. The computational screening of millions of compounds showed a list of several competent ligands. From these ligands they synthesized the compounds with the best docking score, which were further optimized by adding side residues for better interaction with the μOR. A promising compound, PZM21, was a selective agonist of μOR. It has better analgesic properties with minimal side effects of respiratory depression and constipation. This work is a step towards better drug designing and synthesizing in terms of efficacy, specificity with least side effects of targeted GPCR proteins present in the human proteome.
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http://dx.doi.org/10.1186/s13065-018-0383-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803155PMC
February 2018

Increasing the Strength and Production of Artemisinin and Its Derivatives.

Molecules 2018 Jan 3;23(1). Epub 2018 Jan 3.

Department of Chemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia.

Artemisinin is a natural sesquiterpene lactone obtained from the herb. It is widely used for the treatment of malaria. In this article, we have reviewed the role of artemisinin in controlling malaria, spread of resistance to artemisinin and the different methods used for its large scale production. The highest amount of artemisinin gene expression in tobacco leaf chloroplast leads to the production of 0.8 mg/g of the dry weight of the plant. This will revolutionize the treatment and control of malaria in third world countries. Furthermore, the generations of novel derivatives of artemisinin- and trioxane ring structure-inspired compounds are important for the treatment of malaria caused by resistant plasmodial species. Synthetic endoperoxide-like artefenomel and its derivatives are crucial for the control of malaria and such synthetic compounds should be further explored.
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http://dx.doi.org/10.3390/molecules23010100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017432PMC
January 2018

Molecular docking and biological evaluation of some thioxoquinazolin-4(3H)-one derivatives as anticancer, antioxidant and anticonvulsant agents.

Chem Cent J 2017 May 31;11(1):48. Epub 2017 May 31.

Department of Chemistry, Islamia College University Peshawar, Peshawar, 25120, Pakistan.

Background: The quinazoline are an important class of medicinal compounds that possess a number of biological activities like anticancer, anticonvulsant and antioxidant etc.

Results: We evaluated the previously synthesized quinazoline derivatives 1-3 for their anticancer activities against three cancer cell lines (HepG2, MCF-7, and HCT-116). Among the tested compounds, quinazolines 1 and 3 were found to be more potent than the standard drug Vinblastine against HepG2 and MCF-7 cell lines. All the tested compounds had less antioxidant activity and did not exhibit any anticonvulsant activity. Also, molecular docking studies were performed to get an insight into the binding modes of the compounds with human cyclin-dependent kinase 2, butyrylcholinesterase enzyme, human gamma-aminobutyric acid receptor. These compounds showed better docking properties with the CDK2 as compared to the other two enzymes.

Conclusions: The overall study showed that thioxoquinazolines are suitable antitumor agents and they should be explored for other biological activities. Modification in the available lot of quinazoline and synthesis of its novel derivatives is essential to explore the potential of this class of compounds. The increase in the threat and with the emergence of drug resistance, it is important to explore and develop more efficacious drugs.
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http://dx.doi.org/10.1186/s13065-017-0272-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451370PMC
May 2017

Mutations in algal and cyanobacterial Photosystem I that independently affect the yield of initial charge separation in the two electron transfer cofactor branches.

Biochim Biophys Acta Bioenerg 2018 Jan 21;1859(1):42-55. Epub 2017 Oct 21.

School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, USA. Electronic address:

In Photosystem I, light-induced electron transfer can occur in either of two symmetry-related branches of cofactors, each of which is composed of a pair of chlorophylls (ec2/ec3 or ec2/ec3) and a phylloquinone (PhQ or PhQ). The axial ligand to the central Mg of the ec2 and ec2 chlorophylls is a water molecule that is also H-bonded to a nearby Asn residue. Here, we investigate the importance of this interaction for charge separation by converting each of the Asn residues to a Leu in the green alga, Chlamydomonas reinhardtii, and the cyanobacterium, Synechocystis sp. PCC6803, and studying the energy and electron transfer using time-resolved optical and EPR spectroscopy. Nanosecond transient absorbance measurements of the PhQ to F electron transfer show that in both species, the PsaA-N604L mutation (near ec2) results in a ~50% reduction in the amount of electron transfer in the B-branch, while the PsaB-N591L mutation (near ec2) results in a ~70% reduction in the amount of electron transfer in the A-branch. A diminished quantum yield of PPhQ is also observed in ultrafast optical experiments, but the lower yield does not appear to be a consequence of charge recombination in the nanosecond or microsecond timescales. The most significant finding is that the yield of electron transfer in the unaffected branch did not increase to compensate for the lower yield in the affected branch. Hence, each branch of the reaction center appears to operate independently of the other in carrying out light-induced charge separation.
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http://dx.doi.org/10.1016/j.bbabio.2017.10.003DOI Listing
January 2018

Non-invasive strategies for targeting the posterior segment of eye.

Int J Pharm 2017 Sep 26;530(1-2):326-345. Epub 2017 Jul 26.

Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland; Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014 Helsinki, Finland. Electronic address:

The safe and effective treatment of eye diseases has been remained a global myth. Several advancements have been done and various drug delivery and treatment techniques have been suggested. The Posterior segment disorders are the leading cause of visual impairments and blindness. Targeting the therapeutic agents to the anterior and posterior segments of the eye has attracted extensive attention from the scientific community. Significant key factors in the success of ocular therapy are the development of safe, effective, economic and non-invasive novel drug delivery systems. These specialized non-invasive ocular drug delivery systems revolutionized the drug delivery strategies by overcoming the limitations, provided targeted delivery to the ocular tissues by avoiding larger doses, and reducing the toxicity encountered by the conventional approaches. These non-invasive systems are fabricated by ingredients encompassing biodegradability, biocompatibility, mucoadhesion, solubility and permeability enhancement and stimuli responsiveness. The variety of routes are utilized to provide minimally invasive drug delivery to the patients without any discomfort and pain. This review is focused on the brief introduction, types, significance, preparation techniques, components and mechanism of drug release of non-invasive systems, including in situ gelling systems, microspheres, iontophoresis, nanoparticles, nanosuspensions and specialized novel emulsions.
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http://dx.doi.org/10.1016/j.ijpharm.2017.07.065DOI Listing
September 2017

Photosynthesis at the far-red region of the spectrum in Acaryochloris marina.

Biol Res 2017 May 19;50(1):16. Epub 2017 May 19.

Department of Chemistry, College of Science, King Saud University, Riyad, Saudi Arabia.

Acaryochloris marina is an oxygenic cyanobacterium that utilizes far-red light for photosynthesis. It has an expanded genome, which helps in its adaptability to the environment, where it can survive on low energy photons. Its major light absorbing pigment is chlorophyll d and it has α-carotene as a major carotenoid. Light harvesting antenna includes the external phycobilin binding proteins, which are hexameric rods made of phycocyanin and allophycocyanins, while the small integral membrane bound chlorophyll binding proteins are also present. There is specific chlorophyll a molecule in both the reaction center of Photosystem I (PSI) and PSII, but majority of the reaction center consists of chlorophyll d. The composition of the PSII reaction center is debatable especially the role and position of chlorophyll a in it. Here we discuss the photosystems of this bacterium and its related biology.
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http://dx.doi.org/10.1186/s40659-017-0120-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438491PMC
May 2017

Inclusion Complexes of a New Family of Non-Ionic Amphiphilic Dendrocalix[4]arene and Poorly Water-Soluble Drugs Naproxen and Ibuprofen.

Molecules 2017 May 11;22(5). Epub 2017 May 11.

Department of Chemistry, College of Science, King Saud University, Riyadh 11495, Saudi Arabia.

The inclusion complexes of a new family of nonionic amphiphilic calix[4]arenes with the anti-inflammatory hydrophobic drugs naproxen (NAP) and ibuprofen (IBP) were investigated. The effects of the alkyl chain's length and the inner core of calix[4]arenes on the interaction of the two drugs with the calix[4]arenes were explored. The inclusion complexes of Amphiphiles - with NAP and IBP increased the solubility of these drugs in aqueous media. The interaction of - with the drugs in aqueous media was investigated through fluorescence, molecular modeling, and ¹H-NMR analysis. TEM studies further supported the formation of inclusion complexes. The length of lipophilic alkyl chains and the intrinsic cyclic nature of cailx[4]arene derivatives - were found to have a significant impact on the solubility of NAP and IBP in pure water.
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http://dx.doi.org/10.3390/molecules22050783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154630PMC
May 2017

Molecular modeling, simulation and docking study of ebola virus glycoprotein.

J Mol Graph Model 2017 03 19;72:266-271. Epub 2016 Dec 19.

Department of Chemistry, Islamia College University, Peshawar, Khyber Pakhtunkhwa, Pakistan. Electronic address:

Ebola virus (EBOV) is a filamentous, enveloped, non-segmented, negative-strand ribonucleic acid (RNA) virus which belongs to family Filoviridae. Ebola virus includes different glycoproteins each of which plays their roles in different aspects of viral life cycle. In this study secreted glycoprotein (Q7T9E0) of Ebola virus was acquired from Uniprot. The formation of alpha helix and beta sheets of secondary structures were predicted through online servers. Higher flexibility and disordered regions of proteins were determined through RONN, GLOBPLOT and DISSEMBLE. Three dimensional (3D) structure of the protein was built through homology modeling techniques and MOE software. The validation and evaluation of the refined models were determined with two stereochemical tests i-e RAMPAGE and ERRAT servers. Further docking studies of given protein was performed with different derivatives of two antiviral drugs dronedarone and amiodarone through MOE. Docking score and binding affinity of respective derivatives demonstrate that these might be used as protein receptors.
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http://dx.doi.org/10.1016/j.jmgm.2016.12.010DOI Listing
March 2017

The New High Resolution Crystal Structure of NS2B-NS3 Protease of Zika Virus.

Viruses 2017 01 10;9(1). Epub 2017 Jan 10.

Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.

Zika virus (ZIKV) is the cause of a significant viral disease affecting humans, which has spread throughout many South American countries and has also become a threat to Southeastern Asia. This commentary discusses the article "Crystal structure of unlinked NS2B-NS3 protease from Zika virus" published recently in the journal by Zhang et al. of Nanyang Technological University, Singapore. They resolved a 1.58 Å resolution structure of the NS2B-NS3 protease of ZIKV and demonstrated how peptide and non-peptide inhibitors interact with this structure, along with the different conformational states that were observed. This protease crystal structure offers new opportunities for the design and development of novel antiviral drugs used for the treatment and control of ZIKV.
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http://dx.doi.org/10.3390/v9010007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294976PMC
January 2017