Cyanoacetanilides Intermediates in Heterocyclic Synthesis. Part 5: Preparation of Hitherto Unknown 5‐Aminopyrazole and Pyrazolo[1,5‐a]pyrimidine Derivatives Containing Sulfamoyl Moiety

Novel 5‐aminopyrazole and pyrazolo[1,5‐a]pyrimidine derivatives have been synthesized from the readily accessible cyanoacetanilide derivative ( 2 ).     

Synthesis,characterization, and anticancer activity of some azole‐heterocyclic complexes with gold(III), palladium(II), nickel(II), and copper(II) metal ions

Four new complexes of Au(III), Pd(II), Ni(II), and Cu(II) ions were synthesized, derived from a novel heterocyclic ligand (L) that has both triazole and tetrazole rings. The ligand synthesis was through successive steps to achieve both heterocyclic rings. The synthesized compounds were characterized using conventional techniques like infrared, ultra violet—visible and proton/carbon nuclear magnetic resonance spectroscopy, metal and thermal analyses, and molar conductivity. All complexes were suggested to have square planar geometry, gold, nickel, and palladium complexes were salts while copper neutral complexes have the chemical formulas; [AuL₂]Cl.2H₂O, [PdL₂]Cl₂.2H₂O, [NiL₂]Cl₂.2H₂O, and [CuL₂]. The cytotoxic effect was studied on breast cancer cell line (MCF‐7 cell line) at different concentrations by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay method, for the ligand (L) and complexes. The results showed that gold(III) and nickel(II) complexes have the highest cytotoxicity among all compounds against cancer cell lines.     

BPB dye confined growth of surfactant-assisted mesostructured silica matrix fiber optic sensing tracers

Thermally stable surfactant modified silica nano-matrix is synthesized by the sol–gel method at low temperature. The surfactant such as cetyltrimethylammonium bromide (CTAB) assisted silica matrix is encapsulated with bromophenol blue (BPB) for sensing activities. Prepared nano-matrix consists of numerous morphological structures such as a pseudo-spherical, hierarchal and islands. The morphology of mesoporous high surface area matrices is strongly affected by CTAB, BPB dye and the aging conditions that determine the transformation from disordered silica nano-matrix morphologies to ordered encapsulated structures. Furthermore, smooth surface matrices with low surface roughness 1.2 nm, low refractive index 1.36, large pores and small dimensions of heteroatoms contribute to the stable sensing activities. The response of coated fiber optic is determined at dynamic pH range 1–12. The prepared sensor has reversibility/repeatability, stability and fast response time of approximately 0.25 s in basic media. The accuracy of sensing device measurements in household ammonia solution and the borax solution suggested that prepared device has clear potential for daily life usage.     

Designing Multivalent Ligands to Control Biological Interactions: From Vaccines and Cellular Effectors to Targeted Drug Delivery

Multivalent interactions in which multiple ligands on one object bind to multiple receptors on another are commonly found in natural biological systems. In addition, these interactions can lead to increased strength and selectivity when compared to the corresponding monovalent interaction. These attributes have also guided the design of synthetic multivalent ligands to control biological interactions. This review will highlight the recent literature describing the use of multivalent ligand display in the design of vaccines, immunomodulators, cell signaling effectors, and vehicles for targeted drug delivery.     

Scaffold Repurposing of In-House Small Molecule Candidates Leads to Discovery of First-in-Class CDK-1/HER-2 Dual Inhibitors: In Vitro and In Silico Screening

Recently, multitargeted drugs are considered a potential approach in treating cancer. In this study, twelve in-house indole-based derivatives were preliminary evaluated for their inhibitory activities over VEGFR-2, CDK-1/cyclin B and HER-2. Compound 15l showed the most inhibitory activities among the tested derivatives over CDK-1/cyclin B and HER-2. Compound 15l was tested for its selectivity in a small kinase panel. It showed dual selectivity for CDK-1/cyclin B and HER-2. Moreover, in vitro cytotoxicity assay was assessed for the selected series against nine NCI cell lines. Compound 15l showed the most potent inhibitory activities among the tested compounds. A deep in silico molecular docking study was conducted for compound 15l to identify the possible binding modes into CDK-1/cyclin B and HER-2. The docking results revealed that compound 15l displayed interesting binding modes with the key amino acids in the binding sites of both kinases. In vitro and in silico studies demonstrate the indole-based derivative 15l as a selective dual CDK-1 and HER-2 inhibitor. This emphasizes a new challenge in drug development strategies and signals a significant milestone for further structural and molecular optimization of these indole-based derivatives in order to achieve a drug-like property.     

Optimized and validated initial-rate method for the determination of perindopril erbumine in tablets

A simple and sensitive kinetic spectrophotometric method for the determination of perindopril in pharmaceutical preparations is described. The method is based on the interaction of drug with 1-chloro-2,4-dinitrobenzene (CDNB) in dimethylsulfoxide (DMSO) at 40+/-1 degrees C. The reaction is followed spectrophotometrically by measuring the rate of change of the absorbance at 420 nm. Under the optimized experimental conditions, the calibration curve showed a linear relationship over the concentration range of 20-140 microg/ml. The activation parameter such as E(a), deltaH*, deltaS* and deltaG* for this reaction were calculated and found to be 27.31 kJ/mol, 24.69 kJ/mol, -138.84 J/K/mol and 61.50 kJ/mol, respectively. The method has been successfully applied to the determination of perindopril in commercial dosage forms. Statistical comparison of the results with the Abdellatef's spectrophotometric method shows excellent agreement and indicates no significant difference between the methods compared in terms of accuracy and precision.     

Kinetic theory of colloidal suspensions: morphology, rheology, and migration

Smoluchowski kinetic equation governing the time evolution of the pair correlation function of rigid sphericalparticles suspended in a Newtonian fluid is extended to include particle migration. The extended kinetic equation takes into account three types of forces acting on the suspended particles: a direct force generated by an interparticle potential, hydrodynamic force mediated by the host fluid, and the Faxén-type forces bringing about the across-the-streamline particle migration. For suspensions subjected to externally imposed flows, the kinetic equation is solved numerically by the proper generalized decomposition method. The imposed flow investigated inthe numerical illustrations is the Poiseuille flow. Numerical solutions provide the morphology (the pair correlation function), the rheology (the stress tensor), and the particle migration.     

Measurement of B(D+-->K(*0)l(+)nu(l))

Using 13.53 fb(-1) of CLEO data, we have measured the ratios of the branching fractions R(+)(e),R(+)(mu) and the combined branching fraction ratio R(+)(l), defined by R(+)(l)=[B(D+-->K(*0)l(+)nu(l))]/[B(D+-->K-pi(+)pi(+))]. We find R(+)(e)=0.74+/-0.04+/-0.05, R(+)(mu)=0.72+/-0.10+/-0.05, and R(+)(l)=0.74+/-0.04+/-0.05, where the first and second errors are statistical and systematic, respectively. The known branching fraction B(D+-->K-pi(+)pi(+)) leads to B(D+-->K(*0)e(+)nu(e))=(6.7+/-0.4+/-0.5+/-0.4)%, B(D+-->K(*0)mu(+)nu(mu))=(6.5+/-0.9+/-0.5+/-0.4)%, and B(D+-->K(*0)l(+)nu(l))=(6.7+/-0.4+/-0.5+/-0.4)%, where the third error is due to the uncertainty in B(D+-->K-pi(+)pi(+)).     

90-fs stretched-pulse ytterbium-doped double-clad fiber laser

We report ultrashort, high-energy pulse generation from a side-pumped Yb-doped double-clad fiber laser. The laser is operating in the stretched-pulse regime. It directly generates 4.8-ps, 5-nJ pulses that are extracavity compressed to 90 fs.