System biology approach to identify the novel biomarkers in glioblastoma multiforme tumors by using computational analysis.

The most common primary brain tumor in adults is glioblastoma multiforme (GBM), accounting for 45.2% of all cases. The characteristics of GBM, a highly aggressive brain tumor, include rapid cell division and a propensity for necrosis.

Targeting XGHPRT enzyme to manage induced gastric cancer: A multi-pronged machine learning, artificial intelligence and biophysics-based study.

infects the stomach mucosa of over half of the global population and can lead to gastric cancer. This pathogen has demonstrated resistance to many frequently prescribed antibiotics, thereby underscoring the pressing need to identify novel therapeutic targets. The inhibition or disruption of nucleic acid biosynthesis constitutes a promising avenue for either restraining or eradicating bacterial proliferation.

Identification of promising methionine aminopeptidase enzyme inhibitors: A combine study of comprehensive virtual screening and dynamics simulation study.

Methionine aminopeptidase (MetAP) enzymes play a critical role in bacterial cell survival by cleaving formyl-methionine initiators at N-terminal of nascent protein, a process which is vital in proper protein folding. This makes MetAP an attractive and novel antibacterial target to unveil promising antibiotics. In this study, the crystal structure of MetAP was used in structure-based virtual screening of drug libraries such as Asinex antibacterial library and Comprehensive Marine Natural Products Database (CMNPD) to identify promising lead molecules against the enzyme.

Identification of Novel Genes and Pathways of Ovarian Cancer Using a Comprehensive Bioinformatic Framework.

Ovarian cancer (OC) is a significant contributor to gynecological cancer-related deaths worldwide, with a high mortality rate. Despite several advances in understanding the pathogenesis of OC, the molecular mechanisms underlying its development and prognosis remain poorly understood. Therefore, the current research study aimed to identify hub genes involved in the pathogenesis of OC that could serve as selective diagnostic and therapeutic targets.

UPLC-MS/MS Method Development for Simultaneous Estimation of Diclofenac and Resveratrol-Loaded Liposomal Gel Formulation in Mice Skin Model: Application to Dermatokinetic Study.

The current research work describes the development of a simple, fast, sensitive and efficient bioanalytical UPLC/MS-MS method for the simultaneous estimation of diclofenac and resveratrol in mice skin samples. Quetiapine was used as an internal standard (IS). Analytical separation was performed on ACQUITY UPLC C18 Column (2.

Discovery of potential phytochemicals as inhibitors of TcdB, a major virulence factors of .

is a gram-positive bacterium which is associated with different gastrointestinal related infections, and the numbers of cases related to it are continuously increasing in the past few years. Owing to high prevalence and development of resistance towards available antibiotics, it is required to develop new therapeutics to combat infection. The current study was aimed to identify novel phytochemicals that could bind and inhibits the TcdB, an exotoxin which is required for the pathogenesis of bacteria, and hence can be considered as the future drug candidates against .

Integrativesubtractive proteomics, immunoinformatics, docking, and simulation approaches reveal candidate vaccine against Sin Nombre orthohantavirus.

The emergence of Sin Nombre orthohantavirus, an etiological agent of hantavirus cardiopulmonary syndrome, exacerbates the situation and imposes a heavy financial burden on healthcare organizations. Multidrug-resistant forms of the disease are prevalent, and there is currently no licensed commercial vaccine. Due to the numerous limitations of experimental vaccines, vaccines against various bacterial and viral diseases have developed computational vaccine design.

Screening of marine natural products for potential inhibitors targeting biotin biosynthesis pathway in .

Tuberculosis (TB) remains as one of the major public health concerns worldwide. A successful TB control and treatment is very challenging, due to continuing emergence of strains resistant to known drugs. Therefore, the development of new drugs with different chemical and biological approaches is necessary to obtain more efficient anti-tubercular therapeutics.

Molecular and Structural Analysis of Specific Mutations from Saudi Isolates of SARS-CoV-2 RNA-Dependent RNA Polymerase and their Implications on Protein Structure and Drug-Protein Binding.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has stressed the global health system to a significant level, which has not only resulted in high morbidity and mortality but also poses a threat for future pandemics. This situation warrants efforts to develop novel therapeutics to manage SARS-CoV-2 in specific and other emerging viruses in general. This study focuses on SARS-CoV2 RNA-dependent RNA polymerase (RdRp) mutations collected from Saudi Arabia and their impact on protein structure and function.

Development of a Validated UPLC-MS/MS Method for Simultaneous Estimation of Neratinib and Curcumin in Human Plasma: Application to Greenness Assessment and Routine Quantification.

A validated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the first-ever simultaneous analysis of neratinib, curcumin and internal standard (imatinib) using acetonitrile as the liquid-liquid extraction medium. On a BEH C18 (100 mm × 2.1 mm, 1.

Novel and Potential Small Molecule Scaffolds as DYRK1A Inhibitors by Integrated Molecular Docking-Based Virtual Screening and Dynamics Simulation Study.

The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a novel, promising and emerging biological target for therapeutic intervention in neurodegenerative diseases, especially in Alzheimer's disease (AD). The mol database, comprising rare, diverse and unique compounds, was explored for molecular docking-based virtual screening against the DYRK1A protein, in order to find out potential inhibitors. Ligands exhibiting hydrogen bond interactions with key amino acid residues such as Ile165, Lys188 (catalytic), Glu239 (gk+1), Leu241 (gk+3), Ser242, Asn244, and Asp307, of the target protein, were considered potential ligands.

Analyzing the effect of mutations in SARS-CoV2 papain-like protease from Saudi isolates on protein structure and drug-protein binding: Molecular modelling and dynamics studies.

The continuous and rapid development of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus remains a health concern especially with the emergence of numerous variants and mutations worldwide. As with other RNA viruses, SARS-CoV-2 has a genetically high mutation rate. These mutations have an impact on the virus characteristics, including transmissibility, antigenicity and development of drug and vaccine resistance.

Fabrication of Membrane Sensitive Electrodes for the Validated Electrochemical Quantification of Anti-Osteoporotic Drug Residues in Pharmaceutical Industrial Wastewater.

Accurate and precise application of ion-selective electrodes (ISEs) in the quantification of environmental pollutants is a strenuous task. In this work, the electrochemical response of alendronate sodium trihydrate (ALN) was evaluated by the fabrication of two sensitive and delicate membrane electrodes, viz. polyvinyl chloride (PVC) and glassy carbon (GC) electrodes.

Validated Simultaneous Gradient Ultra-Performance Liquid Chromatographic Quantification of Some Proton Pump Inhibitor Drug Residues in Saudi Pharmaceutical Industrial Wastewater.

Monitoring and quantification of active pharmaceutical ingredients (APIs) in the environment constitute important and challenging tasks, as they are directly associated with human health. Three commonly used proton pump inhibitors (PPIs), namely, omeprazole sodium (OMP), pantoprazole sodium (PNT), and lansoprazole sodium (LNZ) are well separated and quantified using ultra-performance liquid chromatography (UPLC) in pharmaceutical industrial wastewater. The separation of the studied drugs was performed on a stationary phase with a Waters column (100 × 2.

Discovery of anti-MERS-CoV small covalent inhibitors through pharmacophore modeling, covalent docking and molecular dynamics simulation.

Middle east respiratory syndrome coronavirus (MERS-CoV) is a fatal pathogen that poses a serious health risk worldwide and especially in the middle east countries. Targeting the MERS-CoV 3-chymotrypsin-like cysteine protease (3CL) with small covalent inhibitors is a significant approach to inhibit replication of the virus. The present work includes generating a pharmacophore model based on the X-ray crystal structures of MERS-CoV 3CL in complex with two covalently bound inhibitors.

Synthesis, characterization, biological evaluation and molecular docking of a new quinazolinone-based derivative as a potent dual inhibitor for VEGFR-2 and EGFR tyrosine kinases.

An efficient process for the preparation of a new ethyl 2-((3-(4-fluorophenyl)-6-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)thio) acetate () was described. The prepared derivative was synthesized using the S-arylation method. Several analytical techniques, such as NMR, Raman and infrared spectroscopy, were used to characterize this compound.

Structure-based virtual screening and molecular dynamics of phytochemicals derived from Saudi medicinal plants to identify potential COVID-19 therapeutics.

Coronavirus disease 2019 (COVID-19) has affected almost every country in the world by causing a global pandemic with a high mortality rate. Lack of an effective vaccine and/or antiviral drugs against SARS-CoV-2, the causative agent, has severely hampered the response to this novel coronavirus. Natural products have long been used in traditional medicines to treat various diseases, and purified phytochemicals from medicinal plants provide a valuable scaffold for the discovery of new drug leads.

Structure Prediction of SPAK C-terminal Domain and Analysis of its Binding to RFXV/I Motifs by Homology Modelling, Docking and Molecular Dynamics Simulation Studies.

Background: The STE20/SPS1-related proline/alanine-rich kinase (SPAK) is a component of WNK-SPAK/OSR1 signaling pathway that plays an essential role in blood pressure regulation. The function of SPAK is mediated by its highly conserved C-terminal domain (CTD) that interacts with RFXV/I motifs of upstream activators, WNK kinases, and downstream substrate, cation- chloride cotransporters.

Objective: To determine and validate the three-dimensional structure of the CTD of SPAK and to study and analyze its interaction with the RFXV/I motifs.

Enzyme immobilization offers a robust tool to scale up the production of longer, diverse, natural glycosaminoglycan oligosaccharides.

Although structurally diverse, longer glycosaminoglycan (GAG) oligosaccharides are critical to understand human biology, few are available. The major bottleneck has been the predominant production of oligosaccharides, primarily disaccharides, upon enzymatic depolymerization of GAGs. In this work, we employ enzyme immobilization to prepare hexasaccharide and longer sequences of chondroitin sulfate in good yields with reasonable homogeneity.

Polymeric fluorescent heparin as one-step FRET substrate of human heparanase.

Heparanase, an endo-β-D-glucuronidase, cleaves cell surface and extracellular matrix heparan sulfate (HS) chains and plays important roles in cellular growth and metastasis. Heparanase assays reported to-date are labor intensive, complex and/or expensive. A simpler assay is critically needed to understand the myriad roles of heparanase.

Immobilization alters heparin cleaving properties of heparinase I.

We report here a novel observation that immobilization of heparinase I on CNBr-activated Sepharose results in heparin degradation properties that are different from heparinase I in the free solution form. Studies over a range of pHs (5-8) and temperatures (5-50°C) as well as under batch and flow conditions show that immobilized heparinase 1 displays altered pH and temperature optima, and a higher propensity for generation of longer chains (hexa- and octa-) with variable sulfation as compared to that in the free form, which is known to yield disaccharides. The immobilized enzyme retained good eliminase activity over at least five cycles of reuse.

Design, Synthesis, and Biological Evaluation of Ester and Ether Derivatives of Antisickling Agent 5-HMF for the Treatment of Sickle Cell Disease.

Candidate drugs to counter intracellular polymerization of deoxygenated sickle hemoglobin (Hb S) continue to represent a promising approach to mitigating the primary cause of the pathophysiology associated with sickle cell disease (SCD). One such compound is the naturally occurring antisickling agent, 5-hydroxymethyl-2-furfural (5-HMF), which has been studied in the clinic for the treatment of SCD. As part of our efforts to develop novel efficacious drugs with improved pharmacologic properties, we structurally modified 5-HMF into 12 ether and ester derivatives.

Heparin depolymerization by immobilized heparinase: A review.

Heparin is a member of the glycosaminoglycan (GAG) family composed of glucosamine and uronic acid units containing O-sulfo, N-acetyl and N-sulfo groups, which are alternating in the chain and linked by 1→4 manner. It is a naturally occurring anticoagulant that prevents the formation of clots and their growth within blood. Certain low molecular weight heparins (LMWHs) are considered as better therapeutic agents than natural heparin because of the reduced side effects and smaller risk of bleeding.

Comparative analysis of INLIGHT™-labeled enzymatically depolymerized heparin by reverse-phase chromatography and high-performance mass spectrometry.

Structural characterization of the microheterogeneity of heparin, heparan sulfate, and other glycosaminoglycans is a major analytical challenge. We present the use of a stable isotope-labeled hydrazide tag (INLIGHT™) with high-resolution/accurate mass (HRAM) reverse-phase LC-MS/MS, which was recently introduced for detailed study of N-glycan heterogeneity, to characterize heparinase-digested heparin (digHep) products without the use of semi-volatile ion pairing reagents. Using both full scan LC-MS and data-dependent LC-MS/MS, we identified 116 unique digHep species, a feat possible because of INLIGHT™ labeling.