Design, synthesis, and cytotoxic evaluation of quinazoline-based derivatives as VEGER-2 inhibitors: comparative study against EGFR kinase activity, induction of apoptosis, and molecular docking study.

A novel series of quinazoline-based compounds were designed and synthesized as modified analogues to certain known VEGFR-2 inhibitors, as an extension of our work on the design and synthesis of new VEGFR-2 inhibitors. The anti-proliferative properties of the synthesized compounds were assessed against three tumor cell lines (MCF-7, HepG-2, and K-562). Compounds 8a (IC = 0.

Phenyltriazole-based sulfonamides: novel dual-target agents against MRSA biofilms and resistant pathogens.

The advent of multidrug-resistant bacteria requires the continuous development of new antimicrobial agents. A series of phenyltriazole-sulfonamide hybrid compounds (16-27) have been synthesized and evaluated for their antimicrobial properties, with a focus on combating resistant bacterial strains such as methicillin-resistant (MRSA) and AB5075. Compounds were synthesized through a multi-step reaction, including alkylation and aminoguanidine substitution, with structural elucidation performed using NMR and elemental analysis.

Design, synthesis, and biological investigation of new thiazole-based derivatives as multi-targeted inhibitors endowed with antiproliferative, antioxidant, and antibacterial properties.

Introduction: A novel series of thiazole-based derivatives and was developed, synthesized, and tested for antiproliferative activity as dual EGFR/VEGFR-2 inhibitors, antioxidants, and antibacterial agents.

Methods: The structures of the new compounds and were validated using NMR spectroscopy and elemental microanalysis. The antiproliferative activity of and was tested against a panel of four cancer cell lines using MTT assay.

GC-MS and HPLC-FLD for sensitive assay of toxic cyclohexylamine in artificial sweetener tablets and human biological fluids.

Cyclohexylamine (CHA) is a precursor in the synthesis of artificial sweeteners cyclamate and its major metabolite. CHA is toxic to the nervous system, kidneys, and liver in animal studies. In the present work, gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-fluorescence detection (HPLC-FLD) were introduced for the first time to the determination of nano-level concentration of CHA in artificial sweetener tablets and human biological fluids.

Ferulic Acid Ameliorates Chromium-Induced Nephrotoxicity: Modulation of PERK/eIF2α/ATF4/CHOP, Nrf2, and Inflammatory Signaling.

Hexavalent chromium (HVC) is a highly toxic heavy metal that induces organ damage especially to the kidney. It induces tubular damage and glomerular dysfunction basically through triggering inflammation, redox imbalance, and apoptotic cell death. The current study aimed at investigating the possible protective ability of ferulic acid (FA) against HVC-induced nephrotoxicity employing male Wistar rats as an experimental model.

Theaflavin alleviates cisplatin-induced nephrotoxicity: Targeting SIRT1/p53/FOXO3a/Nrf2 signaling and the NF-kB inflammatory cascade.

Cisplatin is a widely used chemotherapeutic agent. Nevertheless, a significant fraction of cisplatin-treated patients develops nephrotoxicity which limits cisplatin therapeutic implementation. The current work was devoted to investigate the potential nephroprotective impact of theaflavin against the cisplatin-induced nephrotoxicity using male Wistar rats as a mammalian model.

Rational design and synthesis of novel phenyltriazole derivatives targeting MRSA cell wall biosynthesis.

Antimicrobial resistance in methicillin-resistant (MRSA) is a major global health challenge. This study reports the design and synthesis of novel phenyltriazole derivatives as potential anti-MRSA agents. The new scaffold replaces the thiazole core with a 1,2,3-triazole ring, enhancing antimicrobial efficacy and physicochemical properties.

Alleviation of Copper-Induced Hepatotoxicity by Bergenin: Diminution of Oxidative Stress, Inflammation, and Apoptosis via Targeting SIRT1/FOXO3a/NF-κB Axes and p38 MAPK Signaling.

Despite its biological importance, excess copper induces organ damage, especially to the liver. Disruption of critical signaling cascades that control redox status, inflammatory responses, and cellular apoptosis significantly contributes to the copper-induced hepatotoxicity. The present work explored the hepatoprotective ability of bergenin against the copper-induced hepatotoxicity using male Wistar rats as a mammalian model.

Design and construction of novel pyridine-pyrimidine hybrids as selective COX-2 suppressors: anti-inflammatory potential, ulcerogenic profile, molecular modeling and ADME/Tox studies.

NSAIDs represent a mainstay in pain and inflammation suppression, and their actions are mainly based on inhibiting COX-1 and COX-2 enzymes.Due to the adverse effects of these drugs, especially on the stomach and heart, scientists efforts have been directed to manufacture selective COX-2 without cardiovascular side effects and with minimal effects on the stomach. The cardiovascular side effects are thought to be related to the chemical composition rather than mechanism of action of these drugs.

Cytotoxic and Antioxidant Potential of Forssk Essential Oil Growing in Northern Saudi Arabia.

Essential oils are naturally occurring multicomponent combinations of isoprenoids with distinctive odors that are produced by aromatic plants from mevalonic acid. They are extensively applied in aromatherapy for the treatment of various ailments. To investigate the potential therapeutic value of the ingredients in essential oil (EO), gas chromatography-mass spectrometry (GC-MS) analysis was used for essential oil characterization.

Introducing of novel class of pyrano[2,3-]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation.

Microbiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis of a novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, and hydroxyl groups. All new analogs were characterized with full spectroscopic data.

Halogenated class of oximes as a new class of monoamine oxidase-B inhibitors for the treatment of Parkinson's disease: Synthesis, biochemistry, and molecular dynamics study.

Oximes are the promising structural scaffold for inhibiting monoamine oxidase (MAO)-B. Eight chalcone-based oxime derivatives were synthesized by microwave-assisted technique, and their ability to inhibit human MAO (hMAO) enzymes were tested. All compounds showed higher inhibitory activity of hMAO-B than hMAO-A.

Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential.

COVID-19 infection is now considered one of the leading causes of human death. As an attempt towards the discovery of novel medications for the COVID-19 pandemic, nineteen novel compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed and synthesized via a click reaction based on our previous work. The novel compounds were assessed using an in vitro effect on the growth of SARS-CoV-2 virus-infested Vero cells with different compound concentrations: 1 and 10 μM.

Phenanthroindolizidine Alkaloids Secondary Metabolites Diversity in Medicinally Viable Plants of the Genus .

Plants of the genus have commonly been used in traditional medicine in various communities, especially in the tropical and subtropical regions of climatic zones. Of the nearly 300 species reported in the genus, eight are primarily used in various forms to treat a variety of bodily disorders based on the symptoms. Certain plants from the genus have found use as anti-inflammatory, anti-tumor, anti-allergic, anti-microbial, hypoglycemic, hypolipidemic, anti-oxidant, smooth muscle relaxant, immunomodulatory, and anti-plasmodium agents, as well as free-radical scavengers.

Phthalazone tethered 1,2,3-triazole conjugates: In silico molecular docking studies, synthesis, in vitro antiproliferative, and kinase inhibitory activities.

New phthalazone tethered 1,2,3-triazole derivatives 12-21 were synthesized utilizing the Cu(I)-catalyzed click reactions of alkyne-functionalized phthalazone 1 with functionalized azides 2-11. The new phthalazone-1,2,3-triazoles structures 12-21 were confirmed by different spectroscopic tools, like IR; H, C, 2D HMBC and 2D ROESY NMR; EI MS, and elemental analysis. The antiproliferative efficacy of the molecular hybrids 12-21 against four cancer cell lines was evaluated, including colorectal cancer, hepatoblastoma, prostate cancer, breast adenocarcinoma, and the normal cell line WI38.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, , and mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients.

Screening and Molecular Docking of Bioactive Metabolites of the Red Sea Sponge as Potential Antimicrobial Agents.

Marine sponges create a wide range of bioactive secondary metabolites, as documented throughout the year. Several bioactive secondary metabolites were isolated from different members of species. This study aimed for isolation and structural elucidation of major metabolites in order to investigate their diverse bioactivities such as antimicrobial and anti-biofilm activities.

Design, Synthesis, Molecular Modeling, and Anticancer Evaluation of New VEGFR-2 Inhibitors Based on the Indolin-2-One Scaffold.

A new series of indoline-2-one derivatives was designed and synthesized based on the essential pharmacophoric features of VEGFR-2 inhibitors. Anti-proliferative activities were assessed for all derivatives against breast (MCF-7) and liver (HepG2) cancer cell lines, using sunitinib as a reference agent. The most potent anti-proliferative derivatives were evaluated for their VEGFR-2 inhibition activity.

Wound Healing and Antioxidant Properties of Supported by Metabolomic Profiling and Molecular Docking.

Wounds adversely affect people’s quality of life and have psychological, social, and economic impacts. Herbal remedies of Launaea procumbens (LP) are used to treat wounds. In an excision wound model, topical application of LP significantly promoted wound closure (on day 14, LP-treated animals had the highest percentages of wound closure in comparison with the other groups, as the wound was entirely closed with a closure percentage of 100%, p < 0.

New Sulfamethoxazole Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors: Design, Synthesis, Cytotoxic Activity and Molecular Modeling.

In this study new sulphamethoxazole derivatives (, , and ) were designed and synthesized and their structures were fully characterized and validated using NMR, mass, and IR spectroscopy, as well as elemental analyses. All new derivatives () were assayed against human carbonic anhydrase (hCAs IX and XII) for their inhibitory activities. hCAs IX and XII were chosen due to the fact that CAIX expression is recognized as a hypoxia marker with a poor prognosis in breast cancer.

Phytotoxic effects of dry leachates on germination, seedling growth, photosynthetic performance, and gene expression of economically important crops.

The influence of dry leachates of was tested on the seedling growth, photosynthesis, biochemical attributes, and gene expression of the economically important crops, including wheat ( L.), radish ( L.), barley ( L.

LC/MS Profiling and Gold Nanoparticle Formulation of Major Metabolites from as Antibacterial and Antioxidant Potentialities.

L. is a medicinal plant with culinary and ethnomedical applications. Its biological and phytochemical profiles have been extensively researched.

In Vitro Anti-Proliferative, and Kinase Inhibitory Activity of Phenanthroindolizidine Alkaloids Isolated from .

The phenanthroindolizidine alkaloid (-)-tylophorine has been reported for its significant anticancer activity working through different biomechanistic pathways. The current study aimed to evaluate the anticancer activity of phenanthroindolizidine alkaloids isolated from . Six phenanthroindolizidine alkaloid (compounds -) in addition to septicine (), chlorogenic acid (), and chlorogenic acid methyl ester () were isolated from using different chromatographic techniques including vacuum liquid chromatography (VLC) and preparative high performance liquid chromatography (HPLC).

Chitosan Silver and Gold Nanoparticle Formation Using Endophytic Fungi as Powerful Antimicrobial and Anti-Biofilm Potentialities.

Nanotechnology is emerging as a new technology with encouraging innovations. Global antibiotic use has grown enormously, with antibiotic resistance increasing by about 80 percent. In view of this alarming situation, intensive research has been carried out into biogenic nanoparticles and their antibacterial, antifungal, and antitumor activities.

Design, synthesis, and biological evaluation of novel pyrido-dipyrimidines as dual topoisomerase II/FLT3 inhibitors in leukemia cells.

Dual inhibition of topoisomerase (topo) II and FLT3 kinase, as in the case of C-1311, was shown to overcome the shortcomings of using topo II inhibitors solely. In the present study, we designed and synthesized two series of pyrido-dipyrimidine- and pseudo-pyrido-acridone-containing compounds. The two series were evaluated against topo II and FLT3 as well as the HL-60 promyelocytic leukemia cell line in vitro.