Lepidium sativum Secondary Metabolites (Essential Oils): In Vitro and In Silico Studies on Human Hepatocellular Carcinoma Cell Lines.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the greatest cause of cancer-related death in the world. Garden cress (Lepidium sativum) seeds have been proven to possess extraordinary antioxidant, anti-inflammatory, hypothermic, and analgesic properties. In this study, in vitro cytotoxic efficiency evaluation of L. sativum fractions was performed against two hepatocellular carcinoma cell lines (HuH-7 and HEPG-2), and the expression of some apoptotic genes was explored. In addition, the chemical composition of a potent extract of L. sativum was analyzed using gas chromatography coupled with mass spectrometry. Then, molecular docking analysis was implemented to identify the potential targets of the L. sativum components' most potent extract. Overall, the n-hexane extract was the most potent against the two HCC cell lines. Moreover, these cytotoxicity levels were supported by the significant downregulation of EGFR and BCL2 gene expression levels and the upregulation of SMAD3, BAX, and P53 expression levels in both HuH-7 and HEPG2 cell lines. Regarding L. sativum's chemical composition, GC-MS analysis of the n-hexane extract led to the identification of thirty compounds, including, mainly, hydrocarbons and terpenoids, as well as other volatile compounds. Furthermore, the binding affinities and interactions of the n-hexane fraction's major metabolites were predicted against EGFR and BCL2 molecular targets using the molecular docking technique. These findings reveal the potential use of L. Sativum in the management of HCC.

Efficient drug delivery vehicles of environmentally benign nano-fibers comprising bioactive glass/chitosan/polyvinyl alcohol composites.

Nano-fiber composites have shown promising potential in biomedical and biotechnological applications. Herein, novel nano-fiber composites constituting a blend of polyvinyl alcohol (PVA) and chitosan (CS) along with different weight ratios of nano-bioactive glass (BG) were prepared by electrospinning. Nano-fibers incorporating 10% (by wt.) of BG were uniform, dense and defect-free with a diameter of 20-125 nm. The model osteoporotic drug (Risedronate sodium) was blended with the electrospinning forming solution and the in-vitro drug release was further studied. About 30% of the drug was released after only 30 min and the release pattern was sustained over 96 h. Drug release took place through a two-stage intra-particle diffusion mechanism. BG-incorporated nano-fibers markedly retarded the drug release profile relative to their BG-free counterparts. They also enhanced the drug release efficiency by releasing 93 ± 4% of the drug. The developed nano-fiber composites can be potentially used as drug-delivery vehicles due to their efficiency and sustained drug release capacity.

Phototriggered cytotoxic properties of tricarbonyl manganese(I) complexes bearing α-diimine ligands towards HepG2.

Reaction between bromo tricarbonyl manganese(I) and N,N'-bis(phenyl)-1,4-diaza-1,3-butadiene ligands, bearing different electron-donating and electron-withdrawing groups R = OCH3, Cl, and NO2 in the ortho- and para-positions on the phenyl substituent, afforded [MnBr(CO)3(N-N)] complexes. The influence of the character and position of the substituent on the dark stability and carbon monoxide releasing kinetics was systematically investigated and correlated with the data of the time-dependent density functional theory calculations. The combined UV/Vis and IR data clearly revealed that the aerated solutions of [MnBr(CO)3(N-N)] in either coordinating or noncoordinating solvents are dark stable and the fluctuations observed during the incubation period especially in the case of the nitro derivatives may be attributed to the exchange of the axial bromo ligand with the coordinating solvent molecules. The free ligands and nitro complexes were non-cytotoxic to HepG2 cells under both the dark and illumination conditions. In the dark, Mn(I) compounds, incorporating o-OCH3 and o-Cl, exhibited excellent cytotoxicity with IC50 values of 18.1 and 11.8 µM, while their para-substituted analogues were inactive in the dark and active upon the irradiation at 365 nm with IC50 values of 5.7 and 6.7 µM, respectively.

Cytotoxicity of photoactivatable bromo tricarbonyl manganese(i) compounds against human liver carcinoma cells.

Two series of photoinduced tricarbonyl manganese(i) compounds were prepared from the reaction of [MnBr(CO)3(2-C(H)[double bond, length as m-dash]O)] (2-C(H)[double bond, length as m-dash]O: quinoline-2-carboxaldehyde and pyridine-2-carboxaldehyde) and para-substituted aniline derivatives (X = OH, OCH3, Cl and NO2). Different electron-donating and electron-withdrawing substituents were introduced in the para-position of the phenyl ring to investigate their influence on the stability of the compounds in the dark and the photophysical properties upon illumination at 525 nm. When kept in the dark, the aerated solutions of the complexes in dimethyl sulfoxide (DMSO) and CH2Cl2 were stable. In the solution, the complexes bearing electron-withdrawing substituents, exchange their bromo ligands with DMSO solvent molecules, as evidenced from infrared and UV/Vis studies as well as time-dependent density functional theory (TDDFT) calculations. The complexes were assessed for their cytotoxicity, both in the dark and upon exposure to a 525 nm LED, against the human hepatocarcinoma cell line (HepG2). A marked reduction in the viability of HepG2 cells treated with the complex functionalized with quinoline and methoxy substituent was observed after illumination in a dose-dependent manner, with an IC50 value of 7.1 µM, making it the most phototoxic compound in our study.

Spectroscopic investigation of π-acceptors in the determination and photoinduced degradation of Sulfacetamide.

The presence of expired and unused Sulfacetamide (SA) drug in water led to a global need for the development of effective advanced method for the quantitative analysis and for minimizing its occurrence in the nature. To find new effective photochemical decomposition method close to that obtained by the well-known Fenton reaction, the photodegradation of SA was investigated in presence of dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and/or other common additives at two different wavelengths (365 and 256 nm). The role of DDQ in the degradation process of SA was evaluated in comparison to the other investigated π-acceptor systems (Chloranilic acid (CHL) and Picric acid (PA)). While the photodegradation process of SA was hardly to proceed in the absence of a catalyst and/or additive, addition of DDQ and NaNO2 to the solution of SA induced decomposition of about 94% of SA within 25 min upon the exposure to light source at 256 nm. On the other hand, SA was quantitatively analyzed by recording the absorbance of its charge transfer (CT) products with DDQ, CHL and PA at a certain wavelength. CHL is preferred with concentrated samples of SA, while PA is recommended for diluted samples of SA. SA â†’ DDQ has a widely range of stability over the pH range of 4.5-12.0. While SA â†’ CHL is stable only in the acidic medium (pH = 4.8-5.6), SA â†’ PA is steady in the basic medium (pH = 7.5-11.0). The nature of the DDQ CT complex was investigated in the solid state. The electronic structures of the complexes were studied by calculating the time dependent density functional theory (TDDFT) spectra.

Magnetic activated carbon nanocomposite from Nigella sativa L. waste (MNSA) for the removal of Coomassie brilliant blue dye from aqueous solution: Statistical design of experiments for optimization of the adsorption conditions.

The present work was carried out to evaluate the removal of Coomassie brilliant blue dye by adsorption onto a magnetized activated carbon nanocomposite (MNSA) prepared from Nigella sativa L. (NS) waste. Different techniques, including infrared spectroscopy, scanning electron microscopy, and nitrogen adsorption/desorption, were used to characterize MNSA to investigate its adsorption properties. Adsorption experiments were carried out by simultaneously optimizing four variables that usually present a strong effect in adsorption studies. A full 24 factorial design with 3 central points was used. The four independent variables were the initial pH of the dye solution (pH), the initial dye concentration (Co), the adsorbent mass (m), and the contact time (t). The sorption capacity (q) of the adsorbent and the percentage of dye removal (% Rem) from an aqueous solution were used as the responses of the factorial design. The results indicated that pH, Co, and m were essential factors for the overall optimization of both responses (q and % Rem) and that several interactions of two, three and four factors occurred. Based on the design of the experiments (DOE), the optimized conditions for adsorption were pH = 2.00, Co = 40.0 mg L-1, m = 30.0 mg, and t = 3.0 h. Under these conditions, both responses, q and % Rem, were maximized, with a desirability of 85.54%. The findings of this study could be useful for industrial wastewater treatment systems.

Molecularly imprinted polymers based biomimetic sensors for mosapride citrate detection in biological fluids.

Computational modeling was applied to study the intermolecular interactions in the pre-polymerization mixture and find a suitable functional monomer to use in the design of a new molecularly imprinted polymer (MIP) for mosapride citrate which is considerably a large molecule (as the citrate ion is also included in calculations as it has centers that can take part in interaction with monomer via hydrogen bonding). Based on these calculations, methacyrlic acid (MAA) was selected as a suitable functional monomer. Mosapride citrate selective MIP and a non-imprinted polymer (NIP) were synthesized and characterized using FTIR, TGA and SEM and then incorporated in carbon paste electrodes (CPEs). The designed modified sensor revealed linear responses in the ranges of 1×10-4-8×10-7 and 8×10-7-8×10-8molL-1 with a limit of detection (LOD) of 2.6×10-8molL-1. The results of the sensor exhibited high selectivity over interfering species and could be applied for the determination of mosapride citrate in pure solutions, pharmaceutical preparations, urine and human serum samples.

Anti-proliferative Activities of Metallic Nanoparticles in an in Vitro Breast Cancer Model.

AIMS: To investigate effect of metallic nanoparticles, silver (AgNPs) and gold nanoparticles (AuNPs) as antitumor treatment in vitro against human breast cancer cells (MCF-7) and their associated mechanisms. This could provide new class of engineered nanoparticles with desired physicochemical properties and may present newer approaches for therapeutic modalities to breast cancer in women. MATERIALS AND METHODS: A human breast cancer cell line (MCF-7) was used as a model of cells. Metallic nanoparticles were characterized using UV-visible spectra and transmission electron microscopy (TEM). Cytotoxic effects of metallic nanoparticles on MCF-7 cells were followed by colorimetric SRB cell viability assays, microscopy, and cellular uptake. Nature of cell death was further investigated by DNA analysis and flow cytometry. RESULTS: Treatment of MCF-7 with different concentrations of 5-10nm diameter of AgNPs inhibited cell viability in a dose-dependent manner, with IC50 value of 6.28µM, whereas treatment of MCF-7 with different concentrations of 13-15nm diameter of AuNPs inhibited cell viability in a dose-dependent manner, with IC50 value of 14.48µM. Treatment of cells with a IC50 concentration of AgNPs generated progressive accumulation of cells in the S phase of the cell cycle and prevented entry into the M phase. The treatment of cells with IC50 concentrations of AuNPs similarly generated progressive accumulation of cells in sub-G1 and S phase, and inhibited the entrance of cells into the M phase of the cell cycle. DNA fragmentation, as demonstrated by electrophoresis, indicated induction of apoptosis. CONCLUSIONS: Our engineered silver nanoparticles effectively inhibit the proliferation of human breast carcinoma cell line MCF-7 in vitro at high concentration (1000 µM) through apoptotic mechanisms, and may be a beneficial agent against human carcinoma but further detailed study is still needed.

Individual and competitive adsorption of phenol and nickel onto multiwalled carbon nanotubes.

Individual and competitive adsorption studies were carried out to investigate the removal of phenol and nickel ions by adsorption onto multiwalled carbon nanotubes (MWCNTs). The carbon nanotubes were characterized by different techniques such as X-ray diffraction, scanning electron microscopy, thermal analysis and Fourier transformation infrared spectroscopy. The different experimental conditions affecting the adsorption process were investigated. Kinetics and equilibrium models were tested for fitting the adsorption experimental data. The characterization experimental results proved that the studied adsorbent possess different surface functional groups as well as typical morphological features. The batch experiments revealed that 300 min of contact time was enough to achieve equilibrium for the adsorption of both phenol and nickel at an initial adsorbate concentration of 25 mg/l, an adsorbent dosage of 5 g/l, and a solution pH of 7. The adsorption of phenol and nickel by MWCNTs followed the pseudo-second order kinetic model and the intraparticle diffusion model was quite good in describing the adsorption mechanism. The Langmuir equilibrium model fitted well the experimental data indicating the homogeneity of the adsorbent surface sites. The maximum Langmuir adsorption capacities were found to be 32.23 and 6.09 mg/g, for phenol and Ni ions, respectively. The removal efficiency of MWCNTs for nickel ions or phenol in real wastewater samples at the optimum conditions reached up to 60% and 70%, respectively.

Novel Ni(II) and Zn(II) complexes coordinated by 2-arylaminomethyl-1H-benzimidazole: molecular structures, spectral, DFT studies and evaluation of biological activity.

[NiL(1,2)Cl(2)(OH(2))(3)]·zH(2)O and [ZnL(1,2)(CH(3)CO(2))(2)] (L(1)=(1H-benzimidazol-2-ylmethyl)-N-phenyl amine, z=0 and L(2)=2-[(1H-Benzimidazol-2-ylmethyl)-amino]-benzoic acid methyl ester, z=1) complexes have been synthesized and characterized by a variety of physico-chemical techniques. The central Ni(II) ion is coordinated by only the pyridine-type nitrogen (N(py)) of benzimidazole ring, three water molecules and two chlorido ligands forming a distorted octahedral geometry. Five coordinated zinc complexes were obtained, where the coordination sphere of zinc ion is made up of secondary amino group (NH(sec)), N(py) and two acetate groups, one acts as a unidentate and the other as a bidentate. A theoretical DFT/UB3LYP method combined with LANL2DZ basis set shows that all the metal-ligand bonds are of the L→M type. Electronic structures have been calculated using TD-DFT method. The antibacterial activity of NiL(2) complexes decreases by the introduction of COOCH(3) group in the ortho-position of the aniline moiety.

Construction and performance characteristics of new ion selective electrodes based on carbon nanotubes for determination of meclofenoxate hydrochloride.

This work offers construction and comparative evaluation the performance characteristics of conventional polymer (I), carbon paste (II) and carbon nanotubes chemically modified carbon paste ion selective electrodes (III) for meclofenoxate hydrochloride are described. These electrodes depend mainly on the incorporation of the ion pair of meclofenoxate hydrochloride with phosphomolybdic acid (PMA) or phosphotungestic acid (PTA). They showed near Nernestian responses over usable concentration range 1.0 × 10(-5) to 1.0 × 10(-2)M with slopes in the range 55.15-59.74 mV(concentrationdecade)(-1). These developed electrodes were fully characterized in terms of their composition, response time, working concentration range, life span, usable pH and temperature range. The electrodes showed a very good selectivity for Meclo with respect to a large number of inorganic cations, sugars and in the presence of the degradation product of the drug (p-chloro phenoxy acetic acid). The standard additions method was applied to the determination of MecloCl in pure solution, pharmaceutical preparations and biological samples. Dissolution testing was also applied using the proposed sensors.

Molecular structures of 2-arylaminomethyl-1H-benzimidazole: spectral, electrochemical, DFT and biological studies.

In the present work, structural studies on (1H-benzimidazol-2-ylmethyl)-N-(4-chloro-phenyl)-amine (L(1)) and (1H-benzimidazol-2-ylmethyl)-N-(4-iodo-phenyl)-amine (L(2)) have been done extensively by a variety of physico-chemical techniques. Optimized geometrical structures, harmonic vibrational frequencies, natural bonding orbital (NBO) analysis, and Frontier molecular orbitals (FMO) were obtained by DFT/B3LYP method. TD-DFT calculations help to assign the electronic transitions. The polarizable continuum model (PCM) fails to describe the experimental chemical shift associated with the NH protons as calculated by applying Gauge-invariant atomic orbital (GIAO) method, but a very good correlation between the theoretical and experimental values was achieved by taking into account the specific solute-solvent interactions. DFT calculations showed a good agreement between the theoretical and observed results. These compounds exhibited a high biological activity through the inhibition of the metabolic growth of the investigated bacteria.

Molecular structure of 2-chloromethyl-1H-benzimidazole hydrochloride: single crystal, spectral, biological studies, and DFT calculations.

In the present work, structural studies on 2-chloromethyl-1H-benzimidazole hydrochloride have been performed extensively by X-ray crystallography, (1)H NMR, FT-IR, UV/vis, and elemental analysis. The title compound crystallizes in a monoclinic space group P2(1)/c with a=7.1982 (3) Å, b=9.4513 (5) Å, c=14.0485 (7) Å and ß=102.440 (3)° forming an infinite chain structure parallel to "b" axis through the intermolecular hydrogen bond. Optimized geometrical structure, harmonic vibrational frequencies, natural bonding orbital (NBO) and frontier molecular orbitals (FMO) were obtained by DFT/B3LYP method combined with 6-31G(d) basis set. TD-DFT calculations help to assign the electronic transitions. The (1)H NMR chemical shifts were computed at the B3LYP/6-311+G(2d,p) level of theory in different solvents by applying GIAO method using the polarizable continuum model (PCM). The title compound was screened for its antibacterial activity referring to Tetracycline as a standard antibacterial agent.

Novel palladium(II) and platinum(II) complexes with 1H-benzimidazol-2-ylmethyl-N-(4-bromo-phenyl)-amine: structural studies and anticancer activity.

[MLCl(2)] (L = (1H-benzimidazol-2-ylmethyl)-N-(4-bromo-phenyl)-amine; M = Pd & Pt) and [PdL(OH(2))(2)]∙2X∙zH(2)O (X = Br, I, z = 2; X = SCN, z = 1; X = NO(3), z = 0) complexes have been synthesized as potential anticancer compounds and their structures were elucidated using elemental analysis, spectral, thermal analysis and X-ray powder diffraction. The benzimidazole (L) crystallizes in the space group P2(1)/c with a = 8.6660(3) Å, b = 16.6739(7) Å, c = 9.8611(4) Å and ß = 113.505(3) ° and forms an infinite chain structure with a trans-zigzag type along the crystallographic axis "a", through the intermolecular H-bond. FT-IR and (1)H NMR studies revealed that the ligand L is coordinated to the metal ion via the pyridine-type nitrogen (N(py)) of the benzimidazole ring and secondary amino group (NH(sec)). Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, and (1)H NMR of the benzimidazole L and its complexes were carried out by DFT/B3LYP method combined with 6-31G(d) and LANL2DZ basis sets. Natural bond orbital (NBO) analysis and frontier molecular orbitals (FMO) were performed at B3LYP/LANL2DZ level of theory. The benzimidazole L, in comparison to its metal complexes was screened for its antibacterial activity. The complexes showed cyctotoxic effects against human breast cancer (MCF7), hepatocarcinoma (HepG(2)) and colon carcinoma cells (HCT). The platinum complex (6) exhibited a moderate antitumor activity against MCF7 with IC(50) = 10.2 µM comparing to that reported for cis-platin 9.91 µM.

Structural and in vitro cytotoxicity studies on 1H-benzimidazol-2-ylmethyl-N-phenyl amine and its Pd(II) and Pt(II) complexes.

[MLCl(2)]·zH(2)O (L = (1H-benzimidazol-2-ylmethyl)-N-phenyl amine; M = Pd, z = 0; M = Pt, z = 1) and [PdL(OH(2))(2)]·2X·zH(2)O (X = Br, I, NO(3), z = 0; X = SCN, z = 1) complexes were synthesized as potential anticancer compounds and characterized by elemental analysis, spectral and thermal methods. FT-IR and (1)H NMR studies revealed that the benzimidazole L is coordinated to the metal ions via the pyridine-type nitrogen (N(py)) of the benzimidazole ring and secondary amino group (NH(sec)). Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, and (1)H NMR of the benzimidazole L and its complexes were carried out by density functional theory using B3LYP functional combined with 6-31G(d) and LANL2DZ basis sets. Natural bond orbitals (NBOs) and frontier molecular orbitals were performed at B3LYP/LANL2DZ level of theory. The synthesized ligand, in comparison to its metal complexes was screened for its antibacterial activity. The benzimidazole L is more toxic against the bacterium Staphylococcus aureus (MIC = 58 µg/mL) than the standard tetracycline (MIC = 82 µg/mL). The complexes showed cytotoxicity against breast cancer, Colon Carcinoma, and human heptacellular Carcinoma cells. The platinum complex (6) displays cytotoxicity (IC(50) = 12.4 µM) against breast cancer compared with that reported for cis-platin 9.91 µM.

2-[(1H-benzimidazol-2-ylmethyl)-amino]-benzoic acid methyl ester: crystal structure, DFT calculations and biological activity evaluation.

In the present study, structural properties of 2-[(1H-benzimidazol-2-ylmethyl)-amino]-benzoic acid methyl ester have been studied extensively by spectral methods and X-ray crystallography. Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, NMR and electronic transitions were carried out by DFT using B3LYP functional combined with 6-31G(d) basis set. Natural bond orbitals (NBO) analysis and frontier molecular orbitals were performed at the same level of theory. DFT calculations showed good agreement between the theoretical and experimental values of optimized and X-ray structure as well as between the vibrational and NMR spectroscopy. The title compound was screened for its antibacterial activity referring to Tetracycline as standard antibacterial agent.

Cinchocaine hydrochloride determination by atomic absorption spectrometry and spectrophotometry.

Two sensitive spectrophotometric and atomic absorption spectrometric procedures have been developed for determination of cinchocaine hydrochloride (Cin.Cl) in pure form and in pharmaceutical formulation. The spectrophotometric method was based on formation of an insoluble colored ion-associate between the cited drug and tetrathiocyanatocobaltate (CoTC) or hexathiocyanatochromate (CrTC) which dissolved and extracted in an organic solvent. The optimal experimental conditions for quantitative extraction such as pH, concentration of the reagents and solvent were studied. Toluene and iso-butyl alcohol proved to be the most suitable solvents for quantitative extraction of Cin-CoTC and Cin-CrTC ion-associates with maximum absorbance at 620 and 555 nm, respectively. The optimum concentration ranges, molar absorptivities, Ringbom ranges and Sandell sensitivities were also evaluated. The atomic absorption spectrometric method is based on measuring of the excess cobalt or chromium in the aqueous solution, after precipitation of the drug, at 240.7 and 357.9 nm, respectively. Linear application ranges, characteristic masses and detection limits were 57.99-361.9, 50.40 and 4.22 microg ml(-1) of Cin.Cl, in case of CoTC, while 37.99-379.9, 18.94 and 0.81 microg ml(-1) in case of CrTC.

Determination of ambroxol hydrochloride in pure solutions and some of its pharmaceutical preparations under batch and FIA conditions.

New ambroxol (Amb) ion selective plastic membrane electrodes of both conventional and coated graphite types based on the ion-pair of ambroxolium tetraphenylborate (Amb-TPB) ion-pair are prepared. The conventional type electrode was fully characterized in terms of membrane composition, life span, pH, ionic strength and temperature. It was applied to potentiometric determination of ambroxol in pure solutions and pharmaceutical preparations under batch and flow injection conditions. The potentiometric determination was used in the determination of ambroxol in muco syrup in four batches of different expiry dates, also the amounts of ambroxol released after 1, 8 and 16 h from the muco sustained release type (S.R.) capsules were also assayed. The selectivity of the electrode toward a large number of excipient like inorganic cations, sugars and amino acids was tested. The solubility product of the ion-pair and the formation constant of the precipitation reaction leading to the ion-pair formation were determined conductimetrically.

Flow injection potentiometric determination of amantadine HCl.

New amantadine (Am) ion selective plastic membrane electrodes of both conventional and coated graphite types based on the ion-pair of amantadinium tetraphenylborate (Am-TPB) ion-pair are prepared. The conventional type electrode was fully characterized in terms of membrane composition, life span, pH, ionic strength and temperature. It was applied to potentiometric determination of amantadine in pure state and pharmaceutical preparation under batch and flow injection conditions. The selectivity of the electrode toward a large number of inorganic cations, sugars and amino acids was tested. The solubility product of the ion-pair and the formation constant of the precipitation reaction leading to the ion-pair formation were determined conductimetrically.