Drug protein interaction at the molecular level: A study of sulphonamide carbonic anhydrase complexes

The molecular mechanism of drug action has been studied by X-ray diffraction analysis of human carbonic anhydrase I complexed with two different sulphonamides. The acetazolamide and amino benzene sulphonamide are found to bind to the catalytically essential zinc ion thereby inhibiting the function of the enzyme. The inhibitor molecules are stabilized in the active site of the protein by van der Waals interaction with a number of protein side chain groups.     

Genome-wide profiling of sperm DNA methylation in relation to buffalo (Bubalus bubalis) bull fertility

The DNA methylation pattern in spermatozoa of buffalo bulls of different fertility status was investigated. Spermatozoa isolated DNA from two groups of buffalo bulls (n = 5), selected based on their artificial insemination–generated conception rate data followed by IVF efficiency, were studied for global methylation changes using a custom-designed 180 K buffalo (Bubalus bubalis) CpG island/promoter microarray. A total of 96 individual genes with another 55 genes covered under CpG islands were found differentially methylated in sperm of high-fertile and subfertile buffalo bulls. Important genes associated with biological processes, cellular components, and functions were identified to be differentially methylated in buffalo bulls with differential fertility status. The identified differentially methylated genes were found to be involved in germ cell development, spermatogenesis, capacitation, and embryonic development. The observations hint that methylation defects of sperm DNA may play a crucial role in determining the fertility of breeding bulls. This growing field of sperm epigenetics will be of great benefit in understanding the graded fertility conditions of breeding bulls in commercial livestock production system.     

Health Risk Assessment of Domestic Roof Water Harvesting Using Failure Mode and Effects Analysis: Evidence from Nagaur,Rajasthan, India

This article is crafted around assessment and analysis of health risks associated with domestic rooftop water harvesting in India, with the prime objective of bringing to the forefront the deterrent issues and challenges in rainwater harvesting in general and domestic rooftop water harvesting in particular. This is based on a study on health risk assessment of a domestic rooftop water harvesting project conducted in the Nagaur district of Rajasthan, India, providing a critical reflection and exemplifying the prevalent scenario in the arid regions of the world. The methodology used for deriving the conclusions is failure mode and effects analysis. A set of risks were graded according to their severity based on their risk priority number scores evolved, including various contaminants polluting the harvested rainwater. The findings bear implications for planning of reconstructive changes to be incorporated and thus providing the necessary outlook for effective alleviation of the deterrents and make rainwater harvesting the premium solution for realization of the Millennium Development Goals by providing access to safe drinking water to the populace chiefly in the developing countries where the problem of scarce safe water is grave.     

Monitoring Phase Transformations in Intact Tablets of Trehalose by FT-Raman Spectroscopy

The purpose of this study is to monitor phase transformations in intact trehalose tablets using FT-Raman spectroscopy. Tablets of trehalose dihydrate, amorphous trehalose (obtained by freeze-drying aqueous trehalose solutions), and anhydrous trehalose (β-trehalose) were prepared. The tablets were exposed to different conditions [11% and 0% RH (60°C); 75% RH (25°C)] and monitored periodically over 96 h using Raman spectroscopy. Within 96 h of storage, the following phase transformations were observed: (1) trehalose dihydrate → β-trehalose (11% RH, 60°C), (2) trehalose dihydrate → α-trehalose (0% RH, 60°C), (3) β-trehalose → trehalose dihydrate (75% RH, 25°C), and (4) amorphous trehalose → trehalose dihydrate (75% RH, 25°C). FT-Raman spectroscopy was a useful technique to identify the solid form and monitor multiple-phase transformations in intact trehalose tablets stored at different conditions.     

Discovery of 3-hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles as potent MEK1 inhibitors

3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles were discovered as potent in vitro MEK1 inhibitors.     

Enhanced photodynamic effect of cobalt(III) dipyridophenazine complex on thyrotropin receptor expressing HEK293 cells

Ternary cobalt(III) complexes [CoL(B)] (1-3) of a trianionic tetradentate phenolate-based ligand (L) and phenanthroline bases (B), viz. 1,10-phenanthroline (phen in 1), dipyridoquinoxaline (dpq in 2) and dipyridophenazine (dppz in 3) are synthesized, characterized from X-ray crystallographic, analytical and spectral techniques, and their utility in photodynamic therapy (PDT) of thyroid diseases caused by TSH receptor dysfunction is probed. The complexes display a visible spectral band within the PDT spectral window at ~690 nm. Photodynamic potential was estimated through DNA cleavage activity of the dpq and dppz complexes in UV-A light of 365 nm and red light of 676 nm. The reactions proceed via the hydroxyl radical pathway. The complexes retain their DNA photocleavage activity in red light under anaerobic conditions, a situation normally prevails in hypoxic tumor core. Investigation into the photocytotoxic potential of these complexes showed that the dppz complex 3 is approximately 4-fold more active in the HEK293 cells expressing human thyrotropin receptor (HEK293-hTSHR) than in the parental cell line and has an insignificant effect on an unrelated human cervical carcinoma cell line (HeLa). Photoexcitation of complex 3 in HEK293-hTSHR cells leads to damage hTSHR as evidenced from the decrease in cAMP formation both in absence and presence of hTSH and decrease in the TSHR immunofluorescence with a concomitant cytoplasmic translocation of the membrane protein, cadherin. The involvement of hTSHR is evidenced from the ability of complex 3 to bind to the extracellular domain of hTSHR (hTSHR-ECD) with a K(d) value of 81 nM and from the photocleavage of hTSHR-ECD.     

Substituted biaryl oxazoles,imidazoles, and thiazoles as sodium channel blockers

Voltage-gated sodium channels have been shown to play a critical role in neuropathic pain. With a goal to develop potent peripherally active sodium channel blockers, a series of low molecular weight biaryl substituted imidazoles, oxazoles, and thiazole carboxamides were identified with good in vitro and in vivo potency.     

Biosorptive removal of chromium by husk of Lathyrus sativus: Evaluation of the binding mechanism,kinetic and equilibrium study

The adsorption of tri‐ and hexavalent chromium by the husk of Lathyrus sativus (HLS), which is an agro‐waste has been investigated to find a potential solution to environmental pollution. The pH‐dependent adsorption process finds the optimum values for trivalent and hexavalent chromium ions at about pH 5.0 and pH 2.0, respectively. The process is very fast initially and attains an equilibrium within 90 min following pseudo second‐order rate kinetics. Equilibrium adsorption data can best elucidated by the Langmuir–Freundlich dual model (r² = 0.998) in comparison with other isotherm models examined indicating that both physi‐ and chemisorption are components of the binding mechanism of chromium ions on HLS. The results show that one gram of HLS can adsorb 24.6 mg Cr³⁺ and 44.5 mg Cr⁶⁺. Fourier transform infrared data and functional group modification experiments indicate that –NH₂, ‐COOH, ‐OH, ‐PO₄^3? groups of the biomass interact chemically with the chromium ions. SEM‐energy dispersive X‐ray analysis and X‐ray diffraction spectrum analysis were used to further assess the morphological changes and the mechanisms of chromium ion interaction with HLS. The analysis signified that the biosorption process involved surface morphological changes, complexation and an ion exchange mechanism. The amorphous nature of HLS facilitating metal biosorption was indicated by the X‐ray diffraction analysis.