Correlating physico-chemical properties of analytes with Hansen solubility parameters of solvents using machine learning algorithm for predicting suitable extraction solvent.

Artificial neural networks (ANNs) are biologically inspired algorithms designed to simulate the way in which the human brain processes information. In sample preparation for bioanalysis, liquid-liquid extraction (LLE) represents an important step with the extraction solvent selection is the key laborious step. In the current work, a robust and reliable ANNs model for LLE solvent prediction was generated which could predict the suitable solvent for analyte extraction.

Farnesyl pyrophosphate synthase inhibitors with antiosteoporosis efficacy in ovariectomized rats: A mixed binding approach beyond bisphosphonates.

The primary focus of bisphosphonate medications is on targeting human farnesyl pyrophosphate synthase (hFPPS), an essential regulator of mammalian isoprenoids. Yet, these drugs encounter limitations due to their restricted "druglike" properties and their effectiveness primarily in treating skeletal disorders. In this study, we synthesized novel non-bisphosphonate compounds, using 4,4'-(ethane-1,2-diylbis(oxy))bis(3-methoxybenzaldehyde) (1) as a starting compound, with the aim of targeting hFPPS through a mixed binding approach.

Utilizing experimental design and desirability function in optimizing RP-HPLC method for simultaneous determination of some skeletal muscle relaxants and analgesics.

An experimental design and response surface methodologies using Plackett-Burman and Box-Behnken designs were applied for selecting and optimizing the most appropriate parameters which significantly affect the separation and quantitative estimation of five skeletal muscle relaxants and four analgesic drugs (baclofen, methocarbamol, dantrolene sodium, orphenadrine citrate, cyclobenzaprine hydrochloride, ketoprofen, etoricoxib, ibuprofen, and mefenamic acid) with a relatively short duration of analysis in a single run. For the separation of the nine drugs, an INERTSIL ODS-V3-5 µm C18 column (250 × 4.6 mm I.

Probing benzenesulfonamide-thiazolidinone hybrids as multitarget directed ligands for efficient control of type 2 diabetes mellitus through targeting the enzymes: α-glucosidase and carbonic anhydrase II.

Diabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides 4a-l and 5a-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated for their inhibitory activity against α-glucosidase where most of the compounds showed good to potent activities.

Discovery of novel quinolin-2-one derivatives as potential GSK-3β inhibitors for treatment of Alzheimer's disease: Pharmacophore-based design, preliminary SAR, in vitro and in vivo biological evaluation.

Recently, glycogen synthase kinase-3β (GSK-3β) has been considered as a critical factor implicated in Alzheimer's disease (AD). In a previous work, a 3D pharmacophore model for GSK-3β inhibitors was created and the results suggested that derivative ZINC67773573, VIII, may provide a promising lead for developing novel GSK-3β inhibitors for the AD's treatment. Consequently, in this work, novel series of quinolin-2-one derivatives were synthesized and assessed for their GSK-3β inhibitory properties.

Exploring new quinazolin-4(3H)-one derivatives as CDK2 inhibitors: Design, synthesis, and anticancer evaluation.

In the present work, five series of new 2,3-disubstituted quinazolin-4(3H)-ones 4a-c, 5a-d, 6a-g, 7a,b, and 9a-c were designed, synthesized, and screened in vitro for their cytotoxic activity against 60 cancer cell lines by the National Cancer Institute, USA. Five candidates 4c, 6a, 6b, 6d, and 6g revealed promising cytotoxicity with significant percentage growth inhibition in the range of 81.98%-96.

Successful Management of Severe Unresponsive Snake Bite Envenomation Using Plasmapheresis and Corticosteroid at Egyptian National Environmental and Clinical Toxicology Research Center: A Case Report.

Snakebite is a significant public health issue in which venom-induced consumption coagulopathy is a common and serious complication that results from the activation of the coagulation pathway by snake toxins. We report a male patient, 56 y old, who was thought to have been bitten by a snake on his left foot. He was transported to a nearby hospital where he received analgesics and 3 snake polyvalent antivenom vials, and then he was transported to our hospital after 12 h.

Development and optimization of vildagliptin solid lipid nanoparticles loaded ocuserts for controlled ocular delivery: A promising approach towards treating diabetic retinopathy.

Diabetes mellitus (DM) is the most prevalent cause of diabetic retinopathy (DRP). DRP has been recognized for a long time as a microvascular disease. Many drugs were used to treat DRP, including vildagliptin (VLD).

Discovery of dual kinase inhibitors targeting VEGFR2 and FAK: structure-based pharmacophore modeling, virtual screening, and molecular docking studies.

VEGFR2 and FAK signaling pathways are interconnected and have synergistic effects on tumor angiogenesis, growth, and metastasis. Thus, instead of the conventional targeting of each of these proteins individually with a specific inhibitor, the present work aimed to discover novel dual inhibitors targeting both VEGFR2 and FAK exploiting their association. To this end, receptor-based pharmacophore modeling technique was opted to generate 3D pharmacophore models for VEGFR2 and FAK type II kinase inhibitors.

Successful treatment of intermediate syndrome in a COVID-19 patient with severe organophosphate toxicity.

Organophosphate (OP) poisoning is one of the most common causes of poisoning in the world, due to its easy availability, low cost, and wide occupational exposure. It has a significant death and morbidity rate. Cholinergic syndrome, intermediate syndrome (IMS), and syndrome of delayed polyneuropathy are the three primary syndromes that define OP poisoning.

Novel sulfonamide-phosphonate conjugates as carbonic anhydrase isozymes inhibitors.

The three-components one-pot Kabachnik-Fields reaction of sulfapyridine, diethyl phosphite, and aldehyde under thermal catalysis reaction condition in the presence of bismuth (III) triflate as a catalyst afford the corresponding sulfonamide-phosphonates (3a-3p) in good to excellent yields (78%-91%). The structures of the new synthesized compounds were elucidated and confirmed by variable spectroscopic studies. Single crystal X-ray studies for 3a, 3d, and 3i verified the proposed structure.

Screening for SARS-CoV-2 IgM and IgG antibodies among healthcare workers: A single-center study in Egypt.

Coronavirus disease 2019 (COVID-19) pandemic has become a global public health disaster, spreading throughout the world. In order to accurately determine the extent of the pandemic, it is important to accurately identify the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs). This study intended to determine the prevalence of SARS-CoV-2 infection among HCWs and examine its correlation with the demographic characteristics of the study participants prior to the implementation of the vaccination campaign.

Beneficial role of healthy eating Index-2015 score & physical activity on COVID-19 outcomes.

Background: Nutritional status and physical activity are essential to maintain a strong immune system. No definite pharmacological strategies for Coronavirus disease 2019 treatment are presently available, so natural enhancement of the immune system is in need. Our goal was to assess the correlation of healthy diet and physical activity on COVID-19 disease outcome.

Exploring novel anticancer pyrazole benzenesulfonamides featuring tail approach strategy as carbonic anhydrase inhibitors.

This study aimed to design potent carbonic anhydrase inhibitors (CAIs) based on pyrazole benzenesulfonamide core. Nine series of substituted pyrazole benzenesulfonamide compounds were synthesized with variable groups like sulphamoyl group as in compounds 4a-e, its bioisosteric carboxylic acid as in compounds 5a-e and 8e, ethyl carboxylate ester as in compounds 6a-e and 9a-e, which were designed as potential prodrugs, isothiazole ring as in compound 7, hydrazide derivative 10e, hydroxamic acid derivatives 11a-e and semicarbazide derivatives 12a-c,e. All the synthesized compounds were investigated for their carbonic anhydrase (CA) inhibitory activity against two human CA isoforms hCA IX and hCA XII and compared to acetazolamide (AAZ).

Application of Box-Behnken Design and Response Surface Methodology for Selecting the Optimum RP-HPLC Conditions for the Simultaneous Determination of Paracetamol and Diclofenac Sodium Along With Three Skeletal Muscle Relaxants in Three Different Pharmaceutical Dosage Forms.

An isocratic HPLC method has been developed and validated for estimating paracetamol and diclofenac sodium simultaneously with three skeletal muscle relaxants, namely, methocarbamol, tizanidine hydrochloride and chlorzoxazone in their pure standard mixtures and in different multi-component dosage forms in a single chromatographic run. HPLC separation was achieved on a C18 Inertsil ODS-3V 5 μm column (250 × 4.6 mm) using a mobile phase mixture containing acetonitrile and 25 mM phosphate buffer (pH 7.

Novel VEGFR-2 inhibitors as antiangiogenic and apoptotic agents via paracrine and autocrine cascades: Design, synthesis, and biological evaluation.

Appertaining to its paracrine and autocrine signaling loops, VEGFR-2 succeeded in grabbing attention as one of the leading targets in cancer treatment. Based on the foregoing and our comprehensive studies regarding pharmacophoric features and activity of sorafenib, novel phenylpyridazinone based VEGFR-2 inhibitors 4, 6a-e, 7a,b, 9a,b, 12a-c, 13a,b, 14a,b, 15a,b, and 17a-d were optimized. An assortment of biological assays was conducted to assess the antiangiogenic and apoptotic activities of the synthesized derivatives.

Synthesis and Evaluation of Thioamide and Bromo Derivatives of 1,3-Diphenylpropane-1,3-dione as 5α-Reductase Inhibitors.

Background: 1,3-Diphenylpropane-1,3-dione (1) is an acetylacetone β-diketone in which both of the methyl groups have been replaced with phenyl groups. It is a component of licorice root extract (Glycyrrhiza glabra) and has anti-mutagenic and anti-cancer properties. It functions as a metabolite, an anti-mutagen, and an anti-neoplastic agent.

Design, synthesis, in vitro, and in vivo evaluation of novel phthalazinone-based derivatives as promising acetylcholinesterase inhibitors for treatment of Alzheimer's disease.

Twenty novel phthalazinone-based compounds were designed as acetylcholinesterase (hAChE) inhibitors. Compounds 7e and 17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds 7e and 17c possess minimal toxicity on hepatic and neuroblastoma cell lines.

Design, synthesis, and biological evaluation of furan-bearing pyrazolo[3,4-b]pyridines as novel inhibitors of CDK2 and P53-MDM2 protein-protein interaction.

The novel series of furan-bearing pyrazolo[3,4-b]pyridines were designed as cyclin-dependent kinase 2 (CDK2) inhibitors and as p53-murine double minute 2 (MDM2) inhibitors. The newly synthesized compounds were screened for their antiproliferative activity toward hepatocellular carcinoma (HepG2) and breast cancer (MCF7) cell lines. The most active compounds on both cell lines were additionally evaluated for their in vitro CDK2 inhibitory activity.

Relative CTLA-4, PTPN-22, and interleukin 37 mRNA expressions in patients with lupus nephritis.

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by T-cell immune-dysregulation and loss of tolerance to self-antigens. CTLA-4 and PTPN-22 are involved in the inhibition of T-lymphocytes activation. IL-37 is an anti-inflammatory cytokine that suppresses innate immunity.

Enantioseparation, quantification, molecular docking and molecular dynamics study of five β-adrenergic blockers on Lux-Cellulose-2 column.

Enantioseparation of five β-adrenergic blockers was studied using two mobile phases on a cellulose tris(3-chloro-4-methylphenylcarbamate) (Lux-Cellulose-2) chiral column in normal phase mode. The first mobile phase composed of n-hexane: ethanol: diethylamine 60: 40: 0.1 by volume has successfully resolved the chromatographic peaks of three pairs of β-adrenergic blockers namely, bisoprolol, carvedilol and atenolol.

Dual-target ligand discovery for Alzheimer's disease: triphenylphosphoranylidene derivatives as inhibitors of acetylcholinesterase and β-amyloid aggregation.

Alzheimer disease (AD) is one of the major neurodegenerative diseases that could not be prevented or completely cured and may lead to death. Here, we target AChE and β-amyloid proteins. Synthesising new triphenylphosphporanylidene derivatives based on the surveyed literature and testing their biological activity revealed promising results especially for the acetyl triphenylphosphoranylidene derivative , which showed good inhibitor activity against AChE enzyme with IC in the nanomolar range (97.

Application of Box-Behnken experimental design and response surface methodology for selecting the optimum RP-HPLC conditions for the simultaneous determination of methocarbamol, indomethacin and betamethasone in their pharmaceutical dosage form.

An isocratic RP-HPLC method has been developed for the separation and determination of methocarbamol (MTL), indomethacin (IND), and betamethasone (BET) in combined dosage form using an Inertsil ODS-3v C18 (250 × 4.6 mm, 5 μm) column with UV- detection at 235 nm. Experimental design using Box-Behnken design (BBD) was applied to study the response surface during method optimization and to achieve a good separation with a minimum number of experimental runs.