ABSTRACT
Pyrazolic hybrids appended with naphthalene, p-chlorobenzene, o-phenol and toluene have been synthesized using Claisen Schmidt condensation reaction of 1-benzyl-3,5-dimethyl-1H-pyrazole-4-carbaldehyde. All compounds were characterized by various spectroscopic techniques. Compound (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(4-chlorophenyl)prop-2-en-1-one crystallizes in monoclinic crystal system with C2/c space group. These synthesized compounds were tested for cytotoxic activity and among these compounds 4b and 5a shows prominent cytotoxic activity against triple-negative breast cancer (TNBC) cells MDA-MB-231 with IC50 values 47.72â µM and 24.25â µM, respectively. Distinguishing morphological changes were noticed in MDA-MB-231 cells treated with pyrazole hybrids contributing to apoptosis action. To get more insight into cytotoxic activity, in silico molecular docking of these compounds were performed and the results suggested that (E)-3-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-1-(p-tolyl)prop-2-en-1-one and 1-(1'-benzyl-5-(4-chlorophenyl)-3',5'-dimethyl-3,4-dihydro-1'H,2H-[3,4'-bipyrazol]-2-yl)ethan-1-one binds to the prominent domain of Akt2 indicating their potential ability as Akt2 inhibitor. Moreover, from inâ silico ADME studies clearly demonstrated that these compounds may be regarded as a drug candidate for sub-lingual absorption based on log p values (2.157-4.924). These compounds also show promising antitubercular activity. The overall results suggest that pyrazolic hybrids with substitution at less sterically hindered positions have appealing potent cytotoxic activity and antituberculosis activity due to which they may act as multidrug candidate.
Subject(s)
Antineoplastic Agents , MDA-MB-231 Cells , Molecular Docking Simulation , Molecular Structure , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemistry , Structure-Activity RelationshipABSTRACT
Direct one-pot hydrogenation of furfural (FFR) to cyclopentanone (CPO) was investigated over different silica-supported Pd catalysts. Among these, 4% Pd on fumed silica (4%Pd/f-SiO2) showed remarkable results, achieving almost 98% furfural (FFR) conversion with â¼89% selectivity and 87% yield to cyclopentanone at 165 °C and 500 psig H2 pressure. More interestingly, the fumed-silica-supported catalyst tuned the selectivity toward the rearrangement product, i.e., cyclopentanone, whereas all of the other supports were found to give ring hydrogenation as well as side chain hydrogenation products due to their parent Brönsted acidity and specific support properties. X-ray diffraction data revealed the presence of different phases of the face-centered cubic lattice of metallic Pd along with lowest crystallite size of 15.6 nm in the case of the silica-supported Pd catalyst. However, Pd particle size was found to be in the range of 5-13 nm with even dispersion over the silica support, confirmed by high-resolution transmission electron microscopy analysis. While studying the effect of reaction parameters, it was observed that lower temperature gave low furfural conversion of 58% with only 51% CPO selectivity. Similarly, higher H2 pressure lowered CPO selectivity with subsequent increase in 2-methyl furan and ring hydrogenation product 2-methyl furan and 2-methyl tetrahydrofuran. Thus, as per the requirement, the product selectivity can be tuned by varying the type of support and/or the reaction parameters suitably. With the help of several control experiments and the characterization data, a plausible reaction pathway was proposed for the selective formation of cyclopentanone.
ABSTRACT
The present work describes the improved photocatalytic activity of cetyl trimethylammonium bromide (CTAB)-assisted Bi2WO6 (CBTH) toward the synthesis of bioactive benzazoles. X-ray diffraction analysis of CBTH suggests that crystal growth has occurred along the (200) plane, whereas field-emission scanning electron microscopy images confirm two-dimensional rose bud morphology and high-resolution transmission electron microscopy analysis suggests the formation of thin nanosheets possessing an orthorhombic structure. Temperature-programmed desorption of ammonia and Py-IR measurements indicate substantial acidity with the generation of Brønsted acid sites on the surface of CBTH. Raman spectra of CBTH also corroborate these observations with the formation of defects within [Bi2O2]2+ layers, resulting in decreased thickness and shapes of nanoplates. These beneficial properties are explored toward the photochemical synthesis of benzazoles using a 35 W tungsten lamp and a CBTH photocatalyst, resulting in better yields at lesser exposure time. It is observed that the catalytic activity is retained up to five consecutive cycles with marginal decrease in % yield. Such a feature can be ascribed to the photostability of the photocatalyst even after continuous exposure to light, implying that the surface active sites remained unaltered as evident from the X-ray photoelectron spectroscopy analysis of pre- and post-characterization of CBTH. Moreover, decrease in the surface hydroxyl groups after five catalytic cycles also accounts for the generation of enhanced Brønsted sites owing to the presence of Bi-O on the surface of CBTH. It exhibits better catalytic activity as compared to other photocatalysts employed for the synthesis of benzazoles. Thus, CBTH serves as a robust photocatalyst for the facile synthesis of these heterocycles in a sustainable manner.
ABSTRACT
[This corrects the article DOI: 10.1021/acsomega.7b01086.].
ABSTRACT
Cinnamaldehyde, the bioactive component of the spice cinnamon, and its derivatives have been shown to possess anti-cancer activity against various cancer cell lines. However, its hydrophobic nature invites attention for efficient drug delivery systems that would enhance the bioavailability of cinnamaldehyde without affecting its bioactivity. Here, we report the synthesis of stable aqueous suspension of cinnamaldehyde tagged Fe3O4 nanoparticles capped with glycine and pluronic polymer (CPGF NPs) for their potential application in drug delivery and hyperthermia in breast cancer. The monodispersed superparamagnetic NPs had an average particulate size of â¼ 20 nm. TGA data revealed the drug payload of â¼ 18%. Compared to the free cinnamaldehyde, CPGF NPs reduced the viability of breast cancer cell lines, MCF7 and MDAMB231, at lower doses of cinnamaldehyde suggesting its increased bioavailability and in turn its therapeutic efficacy in the cells. Interestingly, the NPs were non-toxic to the non-cancerous HEK293 and MCF10A cell lines compared to the free cinnamaldehyde. The novelty of CPGF nanoparticulate system was that it could induce cytotoxicity in both ER/PR positive/Her2 negative (MCF7) and ER/PR negative/Her2 negative (MDAMB231) breast cancer cells, the latter being insensitive to most of the chemotherapeutic drugs. The NPs decreased the growth of the breast cancer cells in a dose-dependent manner and altered their migration through reduction in MMP-2 expression. CPGF NPs also decreased the expression of VEGF, an important oncomarker of tumor angiogenesis. They induced apoptosis in breast cancer cells through loss of mitochondrial membrane potential and activation of caspase-3. Interestingly, upon exposure to the radiofrequency waves, the NPs heated up to 41.6 °C within 1 min, suggesting their promise as a magnetic hyperthermia agent. All these findings indicate that CPGF NPs prove to be potential nano-chemotherapeutic agents in breast cancer.
Subject(s)
Acrolein/analogs & derivatives , Antineoplastic Agents/chemistry , Breast Neoplasms/drug therapy , Drug Carriers/chemistry , Magnetite Nanoparticles/chemistry , Acrolein/chemistry , Acrolein/pharmacology , Antineoplastic Agents/pharmacology , Biocompatible Materials , Cell Movement/drug effects , Cell Proliferation , Cell Survival/drug effects , Drug Carriers/pharmacology , Drug Screening Assays, Antitumor , Drug Stability , Female , Glycine/chemistry , HEK293 Cells , Humans , Hyperthermia, Induced , Inhibitory Concentration 50 , Kinetics , MCF-7 Cells , Membrane Potential, Mitochondrial/drug effects , Poloxamer/chemistryABSTRACT
To ascertain the contribution of adsorptive capacity of Montmorillonite (MMT) towards photocatalytic process, CdSe-MMT nanocomposites are explored for adsorptive removal of Indigo Carmine (IC). The nanocomposites are prepared via two approaches: (a) in-situ formation and (b) wet impregnation of CdSe onto MMT support. XRD analysis of composites suggested the proper dispersion of CdSe nanoparticles in MMT clay matrix with spherical morphology of 5-10nm sized CdSe nanoparticles. These nanocomposites are employed for photocatalytic degradation of IC under visible light at various IC concentrations and different amount of catalyst. Kinetics of IC is found to be of pseudo-second order with 10% in-situ and 50% loaded nanocomposites exhibiting better photocatalytic activity at 1.0 g L(-)(1) catalyst and 100 mg L(-)(1)of IC. Dynamics of its adsorptive removal on the composite surface evaluated by employing error estimation tools clearly suggest that Redlich-Peterson and Flory-Huggins adsorption isotherms effectively describe the multi-layer process. It is observed that spontaneous, exothermic chemisorption process occurring on the surface indeed enhances photocatalytic activity. Moreover, such a feature is also found to be associated with diffusion of IC within mesoporous structure of MMT that subsequently favors pore-diffusion controlled adsorption process. IR spectral analysis demonstrated that IC molecule is degraded on the catalyst surface. Light or oxygenated species induced photocorrosion of CdSe is suppressed due to its composite formation with MMT that results in 620 ppm removal of IC during successive cycles; a feature ascribed as improved photocatalytic activity for CdSe nanoparticles.
Subject(s)
Bentonite/chemistry , Cadmium Compounds/chemistry , Indigo Carmine/isolation & purification , Light , Nanocomposites/chemistry , Selenium Compounds/chemistry , Adsorption , Catalysis/radiation effects , Diffusion , Hydrogen-Ion Concentration , Kinetics , Models, Molecular , Nanocomposites/ultrastructure , Nonlinear Dynamics , Recycling , Spectroscopy, Fourier Transform Infrared , Temperature , Time Factors , X-Ray DiffractionABSTRACT
Nanoscale Fe-Pd bimetallic particles were synthesized and used for degradation of lindane (gamma-hexachlorocyclohexane) in aqueous solution. Batch studies showed that 5mg/L of lindane was completely dechlorinated within 5 min at a catalyst loading of 0.5 g/L and the degradation process followed first-order kinetics. GC-MS analysis in corroboration with GC-ECD results showed the presence of cyclohexane as the final degradation product. The proposed mechanism for the reductive dechlorination of lindane involves Fe corrosion-induced hydrogen atom transfer from the Pd surface. The enhanced degradation efficiency of Fe-Pd nanoparticles is attributed to: (1) high specific surface area of the nanoscale metal particles (60 m(2)/g), manyfold greater that of commercial grade micro- or milli-scale iron particles (approximately 1.6m(2)/g); and, (2) increased catalytic reactivity due to the presence of Pd on the surface. Recycling and column studies showed that these nanoparticles exhibit efficient and sustained catalytic activity.
Subject(s)
Chlorine/isolation & purification , Hexachlorocyclohexane/chemistry , Iron/chemistry , Palladium/chemistry , Water Pollutants, Chemical/isolation & purification , Water Purification/methods , Catalysis , Chlorine/chemistry , Gas Chromatography-Mass Spectrometry/methods , Kinetics , Microscopy, Electron, Transmission/methods , Nanoparticles/chemistry , Nanotechnology/methods , Time FactorsABSTRACT
The degradation of Orange G, a monoazo dye, in aqueous solutions was investigated using as-synthesized and stored Fe-Ni bimetallic nanoparticles. Batch experiments with a nanocatalyst loading of 3 g/L showed complete dye degradation (150 mg/L) after 10 min of reaction time. HPLC-MS analysis of the degradation products showed that as-synthesized nanoparticles reductively cleaved the azo linkage to produce aniline as the major degradation product. However, 1-year-stored nanoparticles showed an oxidative degradation of Orange G through a hydroxyl-radical induced coupling of parent and/or product molecules. XPS analysis in corroboration with HPLC-MS data showed that the surface chemistry between Fe and Ni in as-synthesized and stored nanoparticles play a crucial role in directing the mode of degradation. Reductive dye degradation using as-synthesized nanoparticles proceeded through hydride transfer from nickel, whereas formation of a Fe2+ -Ni(0) galvanic cell in stored nanoparticles generated hydroxyl radicals from water in a nonFenton type reaction. The latter were responsible for the generation of radical centers on the dye molecule, which led to a coupling-mediated oxidative degradation of Orange G. The generation of hydroxyl radicals is further substantiated with radical quenching experiments using ascorbic acid indicating that stored nanoparticles degrade Orange G through a predominantly oxidative mechanism. HPLC-MS and XPS analysis of dye degradation using as-synthesized nanoparticles exposed to air and water confirmed that the reductive or oxidative degradation capability of Fe-Ni nanoparticles is decided by the time and type of catalyst aging process.
Subject(s)
Azo Compounds/chemistry , Coloring Agents/chemistry , Iron/chemistry , Nanoparticles/chemistry , Nickel/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Oxidation-Reduction , Water Purification/methodsSubject(s)
Chromatography, High Pressure Liquid/methods , Drug Contamination/prevention & control , Drug Evaluation, Preclinical/methods , Spectrometry, Mass, Electrospray Ionization/methods , Tetrahydroisoquinolines/analysis , Tetrahydroisoquinolines/chemistry , Chromatography, High Pressure Liquid/instrumentation , Ions , Quinapril , Reproducibility of Results , Sensitivity and Specificity , Spectrometry, Mass, Electrospray Ionization/instrumentationABSTRACT
An interesting series of iron (III) complexes with naphthoquinone-thiosemicarbazones are synthesized and physico-chemically characterized by elemental analysis, UV-vis, IR, EPR and magnetic susceptibility measurements. They possess a cationic octahedral [FeL2]+ species and a tetrahedral [FeCl4]- anion and exhibit unusual spin-mixed states involving high-spin and low-spin ferric centers as revealed from magnetic behavior with significant amount of exchange interactions mediated by intermolecular associations. The magnetic susceptibility data is fitted with S1=5/2 and S2=1/2 Heisengberg's exchange coupled model; H=-2JS1S2 and the magnetic exchange interactions are found to be of the order of -13.6 cm-1 indicating the moderate coupling between two paramagnetic centers present in different chemical and structural environment. The presence of spin-paired iron (III) cation having dxz2dxz2dxz1 ground state is revealed from the EPR spectra with three prominent peaks while the high-spin tetrahedral iron (III) anion exhibits characteristics g=4 signal whose intensity increases with lowering the temperature suggesting its influence on the magnetic properties of the complex molecule. FTIR measurements indicate tridentate ONS donor systems involving quinone/hydroxyl oxygen, imine/hydrazinic nitrogen and thione/thiol sulfur atoms as binding sites for naphthoquinone-thiosemicarbazones.
Subject(s)
Iron/chemistry , Naphthoquinones/chemistry , Spin Labels , Thiosemicarbazones/chemistry , Transition Elements/chemistry , Electron Spin Resonance Spectroscopy , Electrons , Ligands , Magnetics , Spectrophotometry, Infrared , TemperatureABSTRACT
The presence of unknown impurity of the order of 0.2% was identified in benazepril using liquid chromatographic technique employing binary gradient system comprising acetic acid and ammonia in water and acetonitrile as the mobile phase. LCMS data corresponds to hydroxylated benazepril (OHB) derivative possessing the molecular formula C(24)H(28)N(2)O(6). This impurity was isolated using isocratic system containing ammonium acetate and acetonitrile and the product was characterized using FT-IR, (1)H and (13)C NMR and mass spectroscopy to ascertain the structure of the impurity. The spectroscopic analysis revealed the presence of hydroxyl function on C(17) carbon atom of benazepril molecule. The plausible mechanism for the formation of OHB species is proposed.