Mechanism of DNA-drug interactions

Over the last two decades many strategies have been planned to design specific drugs for rare diseases to target their action at the DNA level. Advancements in our understanding of the interactions of small nonpeptide molecules with DNA have opened the doors for “rational” drug design. Special methods have now been developed to give accurate account of the precise location of ligand-DNA adducts on target DNA. We are now in a position to think of designing ligands that recognize particular sequences of base pairs. This work will allow us to enter into a new era of gene therapy for diseases like Cystic fibrosis, Alzheimer’s disease and many related disorders at genetic level. These ligands can also be employed in the treatment of various types of cancers. They may also be useful as highly specific probes to locate particular sequences in the genomic DNA.     

Bivalent 3d-metal complexes of malonyl- and succinyldihydrazide based macrocyclic ligands. Synthesis and characterization

Summary The macrocycles 2,10-dimethyl-3,4,8,9,15-pentaazabicyclo-[9.3.1]-pentadeca-1 (15),2,9,11,13-penta-ene-5,7-dione (L) and 2,11-dimethyl-3,4,8,9,10,16-pentaazabicyclo[10.3.1]-hexadeca-1 (16),2,10,12,14-penta-ene-5,8-dione (L) were prepared and characterized by elemental, i.r. and mass spectral data. The macrocycles react with various metal(II) chlorides to yield complexes of the types [MLCl₂H₂O] (M = Mn, Co, Ni, Cu or Zn), [MLCl₂H₂O] (M = Mn, Ni, Cu or Zn) and [Co₃L₂Cl₄]Cl₂. The complexes were characterized by physico-chemical and spectroscopic methods.     

The anionic alkylation of easily reducible arenes. A photochemical route to nucleophilic aromatic substitution of anthracene by organolithiums

High yield nucleophilic addition ensues upon mixing tetrahydrofuran solutions of benzyllithium or cyclooctadienyllithium and anthracene at low temperatures At least part of this addition proceeds by a single electron transfer pathway. Photolysis of the resulting adducts leads to the elimination of lithium hydride, giving net nucleophilic substitution in approximately 50% yield. The analogous reaction fails with naphthalene, where photolysis of the organolithium/ arene mixture leads to dimeric products derived from the organolithium.     

Synthesis of some heterocyclic systems from nucleophilic substitution reactions with η6-o-dichlorobenzene-η5-cyclopentadienyliron hexafluorophosphate

A method for the synthesis of heterocylic systems related to 9,10-dihydroanthracene with two hetero-atoms at the 9,10-positions is described. It involves the nucleophilic substitution reaction of η⁶-o-dichlorobenzene-η⁵-cyclopentadienyliron hexafluorophosphate with two nucleophilic groups (OH, SH and/or NH₂) located in the 1,2-positions of a benzene ring to give a cyclopentadienyliron complexed heterocycle. Upon pyrolytic sublimation of the complex, the free heterocyclic compound is then obtained.     

Superpositions of chiral states in the presence of electric dipole, magnetic dipole, and electric quadrupole interactions

This paper is a straightforward generalization of Maierle-Harris proposal regarding parity implications on the superpositions of chiral states of a molecule. It is shown that the inclusion of electric quadrupole and magnetic dipole interactions removes several of restrictions on the preparation of superpositions of mid R:L and mid R:R states of a chiral molecule. It is also found that the dephasing of mid R:L and mid R:R superpositions, due to the spontaneous emission from the chiral molecule, has opposing contributions from electric quadrupole-magnetic dipole and electric dipole interactions.     

Ionic Interactions of Calcium Sulfate Dihydrate in Aqueous Sodium Chloride Solutions: Solubilities,Densities, Viscosities,Electrical Conductivities,and Surface Tensions at 35 <Superscript>∘</Superscript>C

The thermodynamic, volumetric, transport, and surface properties, solubilities, densities, viscosities, electrical conductivities, and surface tensions of calcium sulfate dihydrate in aqueous sodium chloride solutions have been measured at 35 C, with a view to determine the ionic interactions that occur in these solutions. The experimental density values have been used to calculate the mean apparent molar volumes of the ternary mixtures. Viscosity values have been analyzed using different empirical equations and the experimental values of the viscosity were combined with conductivity to yield the Walden product. Molar surface energies have been computed using experimental surface tension data. The experimental data have been fitted to polynomial equations by a least-squares analysis to obtain the coefficients and their standard errors. Results have been examined in the light of structure making or structure breaking effects of the various ions present in the solutions.     

Use of HPTLC,HPLC, and Densitometry for Qualitative Separation of Indole Alkaloids from Rauvolfia serpentina Roots

JPC – Journal of Planar Chromatography – Modern TLC - High-performance thin-layer chromatography (HPTLC) has been used for normal-phase separation of the components of hexane,...     

Inhibition of human dihydrofolate reductase by 2,4-diaminoquinazolines bearing simple substituents on the aromatic ring

A series of thirty eight 2,4-diaminoquinazolines having diverse substitution patterns on the aromatic ring was evaluated for inhibitory activity against dihydrofolate reductase (DHFR) obtained from a human lymphoblast cell line. Many of these compounds were also evaluated as inhibitors of rat liver DHFR under the same experimental conditions. In most instances the results obtained with each enzyme were comparable indicating that the rodent enzyme is a suitable model for the human DHFR as far as the determination of I₅₀ values is concerned. The results demonstrate that relatively simple 5-substituted- or 5,6-disubstituted-2,4-diaminoquinazolines can be potent DHFR inhibitors. The presence of a nonpolar substituent at position 7 or 8 was highly detrimental to inhibitory potency.     

Comparative Studies of Tridentate Sulfur and Nitrogen‐Containing Ligands as Ionophores for Construction of Cadmium Ion‐Selective Membrane Sensors

New polymeric membrane cadmium‐ion selective sensors have been prepared by incorporating nitrogen and sulfur containing tridentate ligands as the ionophores into the plasticized PVC membranes. Poly(vinyl chloride) (PVC) based membranes of potassium hydrotris[N‐(2,6‐xylyl)thioimdazolyl) borate] (KTt^2,6‐xylyl) and potassium hydrotris(3‐phenyl‐5‐methylpyrazolyl) borate (KTp^Ph,Me) with sodium tetraphenyl borate (NaTPB) as an anionic excluder and dibutylphthalate (DBP), tributylphthalate (TBP), dioctylsebacate (DOS), and o‐nitrophenyloctyl ether (o‐NPOE) as plasticizing solvent mediators were investigated in different compositions. KTt^2,6‐xylyl was found to be a selective and sensitive ion carrier for Cd(II) membrane sensor. A membrane composed of KTt^2,6‐xylyl:NaTPB:PVC:DBP with the % mole ratio 2.3 : 1.1 : 34.8 : 61.8 (w/w) works well over a very wide concentration range (7.8×10^?8–1.0×10^?2 M) with a Nernstian slope of 29.4±0.2 mV/decades of activity between pH values of 3.5 to 9.0 with a detection limit of 4.37×10^?8 M. The sensor displays very good discrimination toward Cd(II) ions with regard to most common cations. The proposed sensor shows a short response time for whole concentration range (ca. 8 s). The effects of the cationic (tetrabutylammonium chloride, TBC), anionic (sodium dodecyl sulfate, SDS) and nonionic (Triton X‐100) surfactants were investigated on the potentiometric properties of proposed cadmium‐selective sensor. The proposed sensor based on KTt^2,6‐xylyl ionophore has also been used for the direct determination of cadmium ions in different water samples and human urine samples.