A Hydrosilylation Approach to Silicon‐Bridged Functional Dipyrromethanes: Introducing Silicon to A New Arena

Two silylene‐spaced ((E)‐vinylsilyl)anthracene‐dipyrromethane dyads have been designed and synthesized by RhCl(PPh₃)₃‐catalyzed hydrosilylation reactions of 5‐methyl‐5′‐(ethynylaryl)dipyrromethanes with (9‐Anthryl)‐dimethylsilane. The complexation studies of dyads toward different anions have also been performed, which reveal that dyads exhibit a highly selective response towards fluoride anion attributable to both hydrogen‐bonding and pentacoordination phenomena. This dual‐mode fluoride recognition event is unprecedented and may pave the way for future developments in the areas of porphyrinoids, organosilicon, polymer, and supramolecular chemistry.     

Assessing G4-Binding Ligands In Vitro and in Cellulo Using Dimeric Carbocyanine Dye Displacement Assay

G-quadruplexes (G4) are the most actively studied non-canonical secondary structures formed by contiguous repeats of guanines in DNA or RNA strands. Small molecule mediated targeting of G-quadruplexes has emerged as an attractive tool for visualization and stabilization of these structures inside the cell. Limited number of DNA and RNA G4-selective assays have been reported for primary ligand screening. A combination of fluorescence spectroscopy, AFM, CD, PAGE, and confocal microscopy have been used to assess a dimeric carbocyanine dye B6,5 for screening G4-binding ligands in vitro and in cellulo. The dye B6,5 interacts with physiologically relevant DNA and RNA G4 structures, resulting in fluorescence enhancement of the molecule as an in vitro readout for G4 selectivity. Interaction of the dye with G4 is accompanied by quadruplex stabilization that extends its use in primary screening of G4 specific ligands. The molecule is cell permeable and enables visualization of quadruplex dominated cellular regions of nucleoli using confocal microscopy. The dye is displaced by quarfloxin in live cells. The dye B6,5 shows remarkable duplex to quadruplex selectivity in vitro along with ligand-like stabilization of DNA G4 structures. Cell permeability and response to RNA G4 structures project the dye with interesting theranostic potential. Our results validate that B6,5 can serve the dual purpose of visualization of DNA and RNA G4 structures and screening of G4 specific ligands, and adds to the limited number of probes with such potential.     

Silica-supported sodium carbonate: an efficient heterogeneous catalyst for the synthesis of new thiazolopyrimidine derivatives

Research on Chemical Intermediates - Herein we describe a new convenient strategy for the synthesis of substituted thiazolopyrimidines. The present approach delivers the use of silica-supported...     

Novel heterocyclic 1,3,4-oxadiazole derivatives of fluoroquinolones as a potent antibacterial agent: Synthesis and computational molecular modeling

Design and synthesis of novel series of 1,3,4-oxadiazoles containing FQs derivatives and screened their antibacterial, antimycobacterial properties. The synthesized compounds were characterized by different spectral techniques like IR, ¹H NMR, ¹³C NMR, mass and elemental analysis. The results of the antimicrobial activity and compounds 6d, 6b, 6e, 6f and 6a demonstrated potent antibacterial activities with zone of inhibition of 42, 36, 37, 34 and 30 mm against S. aureus, E. faecalis, S. pneumoniae, E. coli and K. pneumoniae, respectively. 1,3,4-Oxadiazole derivatives 6a, 6b, 6 g were showed excellent antimycobacterial activity against M. smegmatis H₃₇Rv with MICs 22.35, 16.20, 20.28 µg/mL, respectively. FQs 6d and 6b exhibited highest hydrogen bonding interactions with Asp83 (3.11 A?), Ser80 (2.15 A?) Asp27 (σ-σ), Arg87 (Π-Π), Arg87 (Π-Π), Ser80 (σ-σ), Ala84 (σ-σ) and binding energies ΔG?=????6.41, ??6.97 kcal/mol with active site of topoisomerase-IV from S. pneumoniae [4KPE]. We performed a computational investigation of compounds 6a–j for their absorption, distribution, metabolism and excretion (ADME) properties by using the Molinspiration, Molsoft toolkits. The ligands 6f, 6d and 6b reveal the highest pharmacokinetic properties and possess maximum drug-likeness model score 1.59, 1.46 and 1.23, respectively.

Graphic abstract

     

Identification,control strategies,and analytical approaches for the determination of potential genotoxic impurities in pharmaceuticals: A comprehensive review

Potential genotoxic impurities in pharmaceuticals at trace levels are of increasing concern to both pharmaceutical industries and regulatory agencies due to their possibility for human carcinogenesis. Molecular functional groups that render starting materials and synthetic intermediates as reactive building blocks for small molecules may also be responsible for their genotoxicity. Determination of these genotoxic impurities at trace levels requires highly sensitive and selective analytical methodologies, which poses tremendous challenges on analytical communities in pharmaceutical research and development. Experimental guidance for the analytical determination of some important classes of genotoxic impurities is still unavailable in the literature. Therefore, the present review explores the structural alerts of commonly encountered potential genotoxic impurities, draft guidance of various regulatory authorities in order to control the level of impurities in drug substances and to assess their toxicity. This review also describes the analytical considerations for the determination of potential genotoxic impurities at trace levels and finally few case studies are also discussed for the determination of some important classes of potential genotoxic impurities. It is the authors’ intention to provide a complete strategy that helps analytical scientists for the analysis of such potential genotoxic impurities in pharmaceuticals.     

Synthesis and Biological Studies of O3-Aryl Galactosides as Galectin Inhibitors

β-Galactose derivatives have recently been reported to selectively inhibit galectin-3, and a library of O3-arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3-arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3-trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido-substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins-1, 3, 4 N (N-terminal domain), 4 C (C-terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N- and C-terminal domain of galectin-9 was discovered.     

CHEMICAL STRUCTURE AND FUNCTIONAL PROPERTIES OF AMORPHOUS BORON CARBONITRIDE FILMS

Journal of Structural Chemistry - We report a comprehensive study of the effect of the chemical structure of boron carbonitride films on the variability of their functional characteristics. The...     

Synthesis of Some Novel Bisisoxazolidine Derivatives from Glyoxal‐derived Bisnitrones via Simultaneous Double Cycloaddition Reactions in Water

Simultaneous double 1,3‐dipolar cycloaddition reactions of glyoxal‐derived bisnitrones have been described in water. Significant rate acceleration and improved yields of exclusively diastereoselective and regioselective bisisoxazolidines in water have been observed at room temperature in a short reaction time compared with conventional solvents.     

Liquid chromatography–tandem mass spectrometry method for simultaneous quantification of urapidil and aripiprazole in human plasma and its application to human pharmacokinetic study

A sensitive and selective liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for simultaneous determination of urapidil and aripiprazole in human plasma. A simple liquid–liquid extraction with ethyl acetate was used for the sample preparation. Chromatographic separation was achieved on a Phenomenex C₁₈ (4.6 × 50 mm, 5 µm) column with 0.1% formic acid–acetonitrile (10:90, v/v) as the mobile phase with flow rate of 0.6 mL/min. The quantitation of the target compounds was determined in a positive ion multiple reaction monitoring mode. Calibration plots were linear over the range of 2.0–2503.95 ng/mL for urapidil and 1.0–500.19 ng/mL for aripiprazole. The lower limit of quantitation for urapidil and aripiprazole was 2.0 and 1.0 ng/mL, respectively. Mean recovery was in the range of 69.94–75.62% for both analytes and internal standards. Intra‐day and inter‐day precisions of the assay at three concentrations were 2.56–5.89% with accuracy of 92.31–97.83% for urapidil, and 3.14–6.84% with accuracy of 91.38–94.42% for aripiprazole. The method was successfully applied to human pharmacokinetic study of urapidil and aripiprazole in healthy human male volunteers. Copyright © 2013 John Wiley & Sons, Ltd.