Identification of bicyclic hexafluoroisopropyl alcohol sulfonamides as retinoic acid receptor-related orphan receptor gamma (RORγ/RORc) inverse agonists. Employing structure-based drug design to improve pregnane X receptor (PXR) selectivity

We disclose the optimization of a high throughput screening hit to yield benzothiazine and tetrahydroquinoline sulfonamides as potent RORγt inverse agonists. However, a majority of these compounds showed potent activity against pregnane X receptor (PXR) and modest activity against liver X receptor α (LXRα). Structure-based drug design (SBDD) led to the identification of benzothiazine and tetrahydroquinoline sulfonamide analogs which completely dialed out LXRα activity and were less potent at PXR. Pharmacodynamic (PD) data for compound 35 in an IL-23 induced IL-17 mouse model is discussed along with the implications of a high Y_max in the PXR assay for long term preclinical pharmacokinetic (PK) studies.     

Application of perturbation theory to the nonlinear Volterra-Gause-Witt model for prey-predator interaction

Krylov-Bogoliubov-Mitropolsky perturbation method was used to study the effect of nonlinearity in the Volterra-gause-Witt (VGW) model for a two species prey-predator system. The first order corrections to both the frequency of oscillation and the amplitude of the linearized system were computed. It was found that the basic qualitative features of the nonlinearity are exhibited by the first order result. We have also discussed the Lotka-Volterra problem which is a special case of VGW model.     

Vanadium toxicology – an assessment of general health, haematological aspects and energy response in an Indian catfish Clarias batrachus (Linn)

The pervasive occurrence of vanadium in nature and its use in various industrial processes has increased its inputs in the environment. This has prompted us to elucidate the impact of vanadium on aquatic environ-ment, the primary body for industrial effluent discharge. The energy response of the fish, Clarias batra-chus, its haematological status including haemoglobin (Hb), haematocrit (Ht), leutocrit (Lt), mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV), mean corpuscular haemoglobin concen-tration (MCHC) etc. And overall general health conditions have been observed to be significantly hampered leading to deleterious alterations in the general metabolism of the fish following long term exposure to vana-date. The increase in muscle and tissue lactic acid (2–12 fold) in association with decrease in pyruvic acid (72% in mucle; 26% in liver) reflect a shift towards an anaerobic metabolism of the fish. We conclude that vanadium could be toxic for the fish in question under long term exposure at the doses under observation (2–10 mg L).© Rapid Science 1998     

Optical features of the fluorophore azotobactin: Applications for iron sensing in biological fluids

Siderophores are bio‐organic ligands secreted by microbes to chelate and assimilate iron to meet their metabolic requirements. Siderophores and their analogs have tremendous therapeutic and analytical potential including the use as Fe (III) biosensors; however, only few practical applications have been realized. The aim of this study was the optical and biophysical characterization of the siderophore azotobactin (Az) secreted by the nitrogen‐fixing bacteria Azotobacter vinelandii. The peptide exhibited fluorescence in the visible range. Quantum yield and lifetime in excited state were measured to ascertain the sensitivity of the molecule as a fluorescent marker in biochemical assays. Its high affinity toward iron in the ferric state was demonstrated through fluorescence emission quenching studies. The accuracy of azotobactin as biosensing tool was determined by analyzing the levels of iron in biological fluids, particularly in human serum. Furthermore, it was demonstrated that it can be encapsulated in sol–gel matrices without significant loss of its fluorescence signal, thus enabling it suitable for adaptation to optical biosensor for Fe (III).