Search

A group of new analogs, based on fused thiazole and indazol-2-amine, were created and characterized using various methods such as 1H NMR, 13C NMR, IR, LCMS spectroscopy, and elemental analysisto ascertain the structural configuration and purity of compounds. The inhibitory effects of the synthesized compounds 7a-s and 10a-o were evaluated using human-origincancer cells such as MCF-7 (breast), ME-180 (cervical), and Hep-G2 (liver). Compound 7i exhibited promising activity against the MCF-7, ME-180, and Hep-G2 cancer cell lines among the newly created compounds. The compounds 7a, 7e, 7i, and 7o showed excellent cytotoxicity against MCF-7 cells with IC50values of 15.5±0.3, 12.8±0.6, 11.5±0.8, and 13.7±0.9 μM respectively. The compounds 7a, 7i, 7o, and 7p showed significant cytotoxicity against ME-180 cells with IC50values of 11.6±0.1, 11.5±0.4, 11.5±0.9, and 12.4±0.8 μM respectively. On the other hand, the compounds 7d, 7i, and 7pdemonstrated the highest cytotoxic activity against Hep-G2 cells with IC50values of 10.4±0.2, 12.4±0.5, and 10.6±0.4 μM respectively. The cytotoxicity of the synthesized compounds was compared with Adriamycin, asa reference compound. The outcome of the present investigation may provide a foundation for future studies in developing potent anticancer agents. [ABSTRACT FROM AUTHOR]

Venlafaxine, primarily available in dosage in Venlafaxine hydrochloride (VEN.HCl) form, is a discriminating serotonin and norepinephrine reuptake inhibitor (SNRI) anti-depressant drug. The 4-methoxybenzyl chloride (4-MBC) is a genotoxic impurity present in VEN.HCl. A reverse-phase high-performance liquid chromatography (RP-HPLC) method is developed for the determination of 4-MBC content this method is validated employing ICH (International Council on Harmonisation) guidelines. During the method development, Purospher STAR end-capped (250mmx4.0mm), 5µm HPLC column, and gradient profile for mobile phase with constant 1.0 mL/min flow rate are used. Mobile phase A is a buffer of pH 8.5 containing 0.1% v/v of liquid ammonia in water with adjusted pH using 10% orthophosphoric acid, whereas mobile phase B is acetonitrile. The injection volume, column oven temperature, and autosampler temperature were 50 µL, 55°C, and 5°C, respectively. The data is acquired at 225 nm wavelength. The method yields a well-separated peak of 4-MBC from Venlafaxine and its impurities. This method is linear in the range of LOQ to 150% level of specification concentration of impurity and the observed correlation coefficient is 0.999. The repeatability and intermediate precision are evaluated and the respective values of %RSD for 4-MBC content are 0.43 and 0.93. Robustness studies show insignificant change for the system suitability criteria like %RSD, theoretical plates, and tailing factor, their values being well within the acceptance limit. The new method for the quantification of genotoxic impurity 4-MBC is precise, sensitive, rugged, and accurate; it also qualifies all the criteria of stability, linearity, and robustness. [ABSTRACT FROM AUTHOR]

The metal L-edge (2p → 3d) X-ray absorption spectra are affected by a number of different interactions: electron-electron repulsion, spin-orbit coupling, and charge transfer between metal and ligands, which makes the simulation of spectra challenging. The core restricted active space (RAS) method is an accurate and flexible approach that can be used to calculate X-ray spectra of a wide range of medium-sized systems without any symmetry constraints. Here, the applicability of the method is tested in detail by simulating three ferric (3d5) model systems with well-known electronic structure, viz., atomic Fe3+, high-spin [FeCl6]³- with ligand donor bonding, and low-spin [Fe(CN)6]3- that also has metal backbonding. For these systems, the performance of the core RAS method, which does not require any system-dependent parameters, is comparable to that of the commonly used semi-empirical charge-transfer multiplet model. It handles orbitally degenerate ground states, accurately describes metal-ligand interactions, and includes both single and multiple excitations. The results are sensitive to the choice of orbitals in the active space and this sensitivity can be used to assign spectral features. A method has also been developed to analyze the calculated X-ray spectra using a chemically intuitive molecular orbital picture. [ABSTRACT FROM AUTHOR]

The Baylis-Hillman reaction of 3-O-allyl-[alpha]-D-xylo-pentodialdo-1,4-furanose has produced a diastereomeric mixture of D-gluco- and L-ido-configured [alpha]-methylene-[beta]-hydroxy esters. The [super 1]H NMR of oxepines in [D.sub.2]O has displayed doubling of signals indicating their existence in two different rotamers/conformers.

Hydrogen-bonded interactions in [alpha]-, [beta]- and [gamma]-cyclodextrins (CD) conformers are examined by using the Gauge Invariant Atomic Orbital (GIAO) method within the framework of density functional theory. The conformers of [beta]- and [gamma]-CD having relatively strong secondary hydroxyl interactions are stabilized by solvation from polar solvents.

The hybrid density functional theory is used to study the electronic structure and the molecular electrostatic potentials in [alpha]-, [beta]-, and [gamma]-cyclodextrins (CDs), the cyclic oligomer of glucose having a central cavity of varying sizes. The results obtained from the topography of the molecular electrostatic potential (MESP) provides a measure of the cavity dimensions and explains the formation of the inclusion complexes in these CDs due to the penetration of guest molecules in the cavity.

Dexrabeprazole sodium (DEX•Na) is an active pharmaceutical ingredient and used as proton pump inhibitor. A reverse phase (RP) ultra-performance liquid chromatographic (UPLC) method is developed for determination of related impurities in DEX•Na and this method is validated using ICH guideline. This method was developed using BEH C18 (2.1 X 50 mm) 1.7 µm column and gradient program for mobile phase. Mobile phase A contains 99% phosphate buffer of pH ~7.0 and 1% acetonitrile, where as mobile phase B is the methanol and acetonitrile in 95:5 ratio. The 0.45ml/min. total flow rate, 3.0 µl injection volume, 40°C column oven temperature and 284 nm detection wavelength are used with sampling rate of 5 points per second. The DEX•Na peak is well separated from its known and unknown impurities. The run time of the method is reduced to 10 min. which is ~11 times smaller than methods reported in literature. The method is accurate and precise as well as linear in the range of LOQ to 150% level with respect to specification concentration limit of impurities. The stress conditions to DEX•Na revealed that drug is stable in alkaline medium, while it is sensitive to acidic and oxidative condition. The new method is sensitive, precise, accurate, and rapid; it also qualifies all the criteria of linearity, stability, as well as robustness. [ABSTRACT FROM AUTHOR]

Two new luminescent ruthenium(II) polypyridyl complexes, [Ru(bpy)2(tpt-phen)]Cl2 ( 1; bpy=2,2′-bipyridine, tpt-phen=triptycenyl-1,10-phenanthroline) and [Ru(phen)2(tpt-phen)]Cl2 ( 2; phen=1,10-phenanthroline), have been developed as potential nonviral vectors for DNA delivery. Photophysical and electrochemical properties of the complexes have been investigated and corroborated with electronic structure calculations. DNA condensation by these complexes has been investigated by UV/Vis and emission spectroscopy, circular dichroism spectroscopy, atomic force microscopy, dynamic light scattering, confocal microscopy, and electrophoretic mobility studies. These complexes interact with DNA and efficiently condense DNA into globular nanoparticles that are taken up efficiently by HeLa cells. DNA cleavage inability and biocompatibility of complexes have been explored. Both complexes have good gene transfection abilities. [ABSTRACT FROM AUTHOR]