Synthesis and biological evaluation of 1,2,4-oxadiazole linked 1,3,4-oxadiazole derivatives as tubulin binding agents

As an aspect of our ongoing research in search of new anticancer agents, a series of novel analogs of 1,3,4-oxadiazole embedded with 1,2,4-oxadiazole moieties (11a–j) were synthesized. The structure of the final compounds was confirmed by ¹H NMR, ¹³CNMR and mass spectroscopic techniques and evaluated for their in vitro anticancer activity against three human cancer cell lines (lung, breast). Among the synthesized compounds, 11?b, 11?g, 11?h, and 11i showed potent anticancer activity with IC₅₀ values within the range of 0.34?±?0.025 to 2.45?±?0.23?μM against three human cancer cell lines. Further, these compounds (11a–j) were investigated for molecular docking studies. Among them, compound 11?h showed strong binding affinity on binding sites of target protein EGFR (PDB ID: 4hjo) with highest docking score (-7.028). It revealed that 11?h was a strong tubulin binding agent.     

An efficient microwave-promoted three-component synthesis of thiazolo[3,2-a]pyrimidines catalyzed by SiO2–ZnBr2 and antimicrobial activity evaluation

Chemistry of Heterocyclic Compounds - 2,5-substituted-6-(4-nitrophenyl)-5H-thiazolo[3,2-a]pyrimidin-7-amines. This method, optimized under microwave conditions, was highly efficient and...     

Syntheses,X-ray structures,electrochemical properties and biological evaluation of mono- and dinuclear N2O2-donor ligand-Fe systems

Transition Metal Chemistry - The present work reports the synthesis, spectroscopic and structural characterizations of Fe(III) complexes of types [Fe(L)(H2O)(NCS)] (1),...     

Synthesis,spectral characterization,docking studies and biological activity of urea,thiourea, sulfonamide and carbamate derivatives of imatinib intermediate

Molecular Diversity - A series of new urea/thiourea derivatives 3a–j were synthesized by simple addition reaction of functionalized phenyl isocyanates/isothiocyanates 2a–j with...     

TSP aerosol source apportionment in the urban region of the Indian steel city,Rourkela

Steel industries are a major contributor to aerosols in steel cities like Rourkela.We designed an air quality sampling program to characterize total suspended particulate(TSP) aerosol in urban areas of Rourkela and to identify their steel-related and other sources.Monitoring was carried out over 8 h,twice per week from January 2011 to December 2012.Metallic species of TSP aerosols were analyzed using an atomic absorption spectrophotometer;ionic species using the IS 3025 method;and carbonaceous species using a total organic carbon analyzer.Enrichment factor and Spearman’s rank correlation analysis were carried out on compositional data.Significant seasonal variations were observed for TSP with totals in summer>spring>winter>monsoon.Low concentrations during monsoon reflected wet scavenging,while high concentrations during summer were related to wind turbulence and low humidity.The chemical mass balance model CMB8.2 was applied to apportion sources.Particles related to steel production,road dust,and soil were dominant in all seasons.A fertilizer plant was found to contribute particles in summer and monsoon.Wood combustion,diesel exhaust,and liquefied petroleum gas contributed significantly in spring and winter.While diesel exhaust,industrial manufacturing,solid waste burning,cement kilns,and construction were found to contribute to TSP at various times throughout the year.     

Simultaneous quantitation of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib in plasma by high-performance liquid chromatography with UV detection

A specific, accurate, precise and reproducible high performance liquid chromatography (HPLC) method was developed and validated for the simultaneous quantitation of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib in human plasma. The method employed a simple liquid-liquid extraction of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide and celecoxib and internal standard (IS, DRF-4367) from human plasma (500 microL) into acetonitirile. The organic layer was separated and evaporated under a gentle stream of nitrogen at 40 degrees C. The residue was reconstituted in the mobile phase and injected onto a Kromasil KR 100-5C18 column (4.6 x 250 mm, 5 microm). The chromatographic separation was achieved by gradient elution consisting of 0.05 M formic acid (pH 3)-acetonitrile-methanol-water at a flow rate of 1.0 mL/min. The eluate was monitored using an ultraviolet (UV) detector set at 235 nm. The ratio of peak area of each analyte to IS was used for quantification of plasma samples. Nominal retention times of etoricoxib, salicylic acid, valdecoxib, ketoprofen, nimesulide, IS and celecoxib were 15.63, 17.20, 21.66, 24.95, 26.27, 30.24 and 32.22 min, respectively. The standard curve for etoricoxib, salicylic acid, valdecoxib, ketoprofen and celecoxib was linear (r2 > 0.999) in the concentration range 0.1-50 microg/mL and for nimesulide (r2 > 0.999) in the concentration range 0.5-50 microg/mL. Absolute recovery was >83% from human plasma for all the analytes and IS. The lower limit of quantification (LLOQ) of nimesulide was 0.5 microg/mL and for etoricoxib, salicylic acid, valdecoxib, ketoprofen and celecoxib the LLOQ was 0.1 microg/mL. The inter- and intra-day precisions in the measurement of QC samples, 0.1, 0.3, 15.0 and 40.0 microg/mL (for all analytes except nimesulide), were in the range 2.29-9.37% relative standard deviation (RSD) and 0.69-10.28% RSD, respectively. For nimesulide the inter- and intra-day precisions in the measurement of quality control (QC) samples, 0.5, 1.5, 15.0 and 40.0 microg/mL, were in the range 3.21-7.37% RSD and 0.97-7.06% RSD, respectively. Accuracy in the measurement of QC samples for all analytes was in the range 91.03-106.38% of the nominal values. All analytes including IS were stable in the battery of stability studies, viz. bench top, autosampler and freeze-thaw cycles. Stability of all analytes was established for 21 days at -20 degrees C. The application of the assay in an oral pharmacokinetic study in rats co-administered with celecoxib and valdecoxib is described.     

Synthesis,Anti-Microbial Activity,and Docking Studies of Novel N-Pyridine Substituted 2-Chlorothieno[2,3-d]pyrimidine Derivatives

Russian Journal of General Chemistry - A series of novel N-pyridine substituted 2-chloro-thieno[2,3-d]pyrimidin-4-amine derivatives has been synthesized and characterized by 1H and 13C NMR...