Caryota mitis Lour. palm belongs to Family: Arecaceae. Pyridine and piperidine alkaloids are the most bioactive secondary metabolites reported in this Family. The dried leaves of Caryota mitis Lour. were subjected to defatting using n-hexane. The alkaloids were extracted from the defatted powder (marc) by acid base method. Eight pyridine/ piperidine alkaloids were detected by LC-MS and reported for the first time in the genus Caryota. The alkaloid fraction as well as other plant extract fractions showed antibacterial and antifungal activities (MIC) against selected strains.

Caryota mitis Lour. palm belongs to Family: Arecaceae. Pyridine and piperidine alkaloids are the most bioactive secondary metabolites reported in this Family. The dried leaves of Caryota mitis Lour. were subjected to defatting using n-hexane. The alkaloids were extracted from the defatted powder (marc) by acid base method. Eight pyridine/ piperidine alkaloids were detected by LC-MS and reported for the first time in the genus Caryota. The alkaloid fraction as well as other plant extract fractions showed antibacterial and antifungal activities (MIC) against selected strains.

Caryota mitis Lour. palm belongs to Family: Arecaceae. Pyridine and piperidine alkaloids are the most bioactive secondary metabolites reported in this Family. The dried leaves of Caryota mitis Lour. were subjected to defatting using n-hexane. The alkaloids were extracted from the defatted powder (marc) by acid base method. Eight pyridine/ piperidine alkaloids were detected by LC-MS and reported for the first time in the genus Caryota. The alkaloid fraction as well as other plant extract fractions showed antibacterial and antifungal activities (MIC) against selected strains.

A comparative study of two types of silver nanoparticles was investigated. The effect of the surface chemistry of the studied silver nanoparticles (AgNPs) on their localized surface plasmon resonance was utilized for the quantitative determination of muscle relaxant tizanidine drug. The studied AgNPs are classified according to the type of stabilizing agent used in their synthesis into electrostatically and sterically stabilized AgNPs. The electrostatically-stabilized AgNPs (AA AgNPs) were prepared using ascorbic acid as both reducing and protective agents in alkaline medium. The sterically-stabilized AgNPs type (PEG-AA AgNPs) was prepared using ascorbic acid as a reducing agent and polyethylene glycol as a stabilizing agent at room temperature. The interaction of tizanidine with AgNPs was characterized using four different techniques including, transmission electron microscope, UV–visible spectrophotometric, surface enhanced Raman spectroscopic (SERS) and electroanalytical methods. SERS method was developed to study the relationship between the plasmon resonance and the enhanced power of Raman signal. The electrocatalytic behavior and the interfacial properties of AgNPs were studied using cyclic voltammetry and electrochemical impedance spectroscopy (EIS) on glassy carbon electrode modified with AgNPs. The quantitative determination of tizanidine in pharmaceutical and biological samples was successfully achieved by using AgNPs probe based on spectrophotometric methods. A linear response over the range 10–400 nmol L−1 was obtained. Validation procedures were carried out following International Conference on Harmonization (ICH) guidelines.

Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs, although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry. We describe a systematic and rational computational approach for the identification of covalently binding fragments from compound collections inhibiting enteroviral 3C protease, a target with high therapeutic potential. By implementing reactive groups potentially forming covalent bonds as a chemical feature in our 3D pharmacophore methodology, covalent binders were discovered by high-throughput virtual screening. We present careful experimental validation of the virtual hits using enzymatic assays and mass spectrometry unraveling a novel, previously unknown irreversible inhibition of the 3C protease by phenylthiomethyl ketone-based fragments. Subsequent synthetic optimization through fragment growing and reactivity analysis against catalytic and noncatalytic cysteines revealed specific irreversible 3C protease inhibition.

Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs, although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry. We describe a systematic and rational computational approach for the identification of covalently binding fragments from compound collections inhibiting enteroviral 3C protease, a target with high therapeutic potential. By implementing reactive groups potentially forming covalent bonds as a chemical feature in our 3D pharmacophore methodology, covalent binders were discovered by high-throughput virtual screening. We present careful experimental validation of the virtual hits using enzymatic assays and mass spectrometry unraveling a novel, previously unknown irreversible inhibition of the 3C protease by phenylthiomethyl ketone-based fragments. Subsequent synthetic optimization through fragment growing and reactivity analysis against catalytic and noncatalytic cysteines revealed specific irreversible 3C protease inhibition.

Lead structure discovery mainly focuses on the identification of noncovalently binding ligands. Covalent linkage, however, is an essential binding mechanism for a multitude of successfully marketed drugs, although discovered by serendipity in most cases. We present a concept for the design of fragments covalently binding to proteases. Covalent linkage enables fragment binding unrelated to affinity to shallow protein binding sites and at the same time allows differentiated targeted hit verification and binding location verification through mass spectrometry. We describe a systematic and rational computational approach for the identification of covalently binding fragments from compound collections inhibiting enteroviral 3C protease, a target with high therapeutic potential. By implementing reactive groups potentially forming covalent bonds as a chemical feature in our 3D pharmacophore methodology, covalent binders were discovered by high-throughput virtual screening. We present careful experimental validation of the virtual hits using enzymatic assays and mass spectrometry unraveling a novel, previously unknown irreversible inhibition of the 3C protease by phenylthiomethyl ketone-based fragments. Subsequent synthetic optimization through fragment growing and reactivity analysis against catalytic and noncatalytic cysteines revealed specific irreversible 3C protease inhibition.

Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in differentmatrices. The designed sensor was based on 3D spinel ferromagnetic NiFe2O4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe2O4/ MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites,RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe2O4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4–350 ng mL-1) with LOD of 0.133 ng mL-1. Additionally, the proposed sensor demonstrated good selectivity,stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors.

Novel and sensitive electrochemical sensor was fabricated for the assay of anti-HCV ledipasvir (LEDV) in differentmatrices. The designed sensor was based on 3D spinel ferromagnetic NiFe2O4 nanospheres and reduced graphene oxide (RGO) supported by morpholinium acid sulphate (MHS), as an ionic liquid (RGO/NSNiFe2O4/ MHS). This sensor design was assigned to synergistically tailor the unique properties of nanostructured ferrites,RGO, and ionic liquid to maximize the sensor response. Electrode modification prevented aggregation of NiFe2O4, increasing electroactive surface area and allowed remarkable electro-catalytic oxidation of LEDV with an enhanced oxidation response. Differential pulse voltammetry was used for detection LEDV in complex matrices whereas; cyclic voltammetry and other techniques were employed to characterize the developed sensor properties. All experimental factors regarding sensor fabrication and chemical sensing properties were carefully studied and optimized. Under the optimum conditions, the designated sensor displayed a wide linear range (0.4–350 ng mL-1) with LOD of 0.133 ng mL-1. Additionally, the proposed sensor demonstrated good selectivity,stability and reproducibility, enabling the quantitative detection of LEDV in Harvoni® tablets, human plasma and in a pharmacokinetic study. Our findings suggest that the developed sensor is a potential prototype material for fabrication of high-performance electrochemical sensors.

A series of novel compounds carrying pyrazino[1,2-a]indol-1(2H)-one scaffold (5a-g) and their reaction intermediates, indole-2-carboxamides, (3a-g) were synthesized and evaluated for their ability to inhibit reactive oxygen species (ROS) generation, antioxidant activity and anticancer activity against a panel of cancer cell lines using MTT assay. The results showed that these compounds can inhibit ROS generation during the metabolic phase of phagocytosis in a dose-dependent manner where compounds 5d and 5e were the most potent samples with higher inhibitory activities (IC50 values 3.3 and 1.4 µM, respectively) than that of the reference acetylsalicylic acid (IC50 ¼ 9.7 µM). Results for the determination of potential antioxidant properties of the synthesized compounds showed that compounds 5d and 5e containing pyrazino[1,2-a]indol-1-one backbone were the most acive and even comparable to Trolox. Compounds 3d-f and 5d-f with the least IC50 values in MTT assay were tested against three known anticancer targets EGFR, BRAF and Tubulin. Histopathological and immunohistochemical study were performed to determine the consequence of exposure to chronic low dose of chlorpyrifos on the testis of male mice and results revealed that these effects can be ameliorated by co-treatment with the most active antioxidant compounds 5d and 5e. Finally, molecular docking studies were performed to explore the binding mode of the most active compounds against EGFR and BRAF kinases.