Synthesis, Anticancer Evaluation and in Silico Studies of 1,4-Dihydropyridines.

An efficient 1,4-dihydropyridine synthesis under mild conditions has been developed. Numerous substrates were tested, with yields of 1,4-dihydropridines ranging from good to excellent and a wide range of functional group tolerance. A549, HT-29, and HepG2 cancer cells were used to investigate the anticancer efficacy of each of the produced compounds. Additionally, in-silico docking studies were conducted to understand the structure-based features of the anticancer mechanism with the cancer medication target of Adenosine A2A receptor as well as the molecular level interactions of the compounds.

Investigation on Inorganic Salts K2TiF6 and KBF4 to Develop Nanoparticles Based TiB2 Reinforcement Aluminium Composites.

In the current research, AA6082 aluminium alloy matrix composites (AAMCs) incorporated with various weight fractions of titanium diboride (0, 3, 6, and 9 wt%) were prepared via an in situ casting technique. The exothermic reaction between inorganic powders like dipotassium hexafluorotitanate (K2TiF6) and potassium tetrafluoroborate (KBF4) in molten Al metal contributes to the development of titanium diboride content. The manufactured AA6082-TiB2 AAMCs were evaluated using a scanning electron microscope (SEM) and X-ray diffraction (XRD). The mechanical properties and wear rate (WR) of the AAMCs were investigated. XRD guarantees the creation of TiB2 phases and proves the nonappearance of reaction products in the AMCs. SEM studies depict the even dispersion of TiB2 in the matrix alloy. The mechanical and tribological properties (MTP) of the AAMCs showed improvement by the dispersion of TiB2 particles. The WR decreases steadily with TiB2 and the least WR is seen at nine weight concentrations of TiB2/AA6082 AAMCs. Fabricated composites revealed 47.9% higher flexural strength and 14.2% superior compression strength than the base AA6082 alloy.

The potential of using low cost naturally available biogenic substrates for biological removal of chlorophenol.

This study details the application of naturally available biogenic substrates (NABS) in microbial degradation of 2-chlorophenol (CP). Jatropha deoiled cakes (JDC) and Karanja deoiled cakes (KDC) are used as NABS. The potential of NABS is compared with standard biogenic substrate, glucose. The study was carried out with both acclimatized mixed culture and pure culture, Pseudomonas putida. Microbial activity of the culture was monitored by measuring reduction in chlorophenol concentration, COD, toxicity and Cl(-) ions evolution. The study was carried out for a total of 42days. It was observed that culture having NABS has shown similar chlorophenol reduction but higher COD and toxicity reduction. Amongst NABS, Jatropha deoiled cake (JDC) has shown superior results of 71% COD reduction compared to glucose and KDC. This study is one of the first kind illustrating the potential of these substrates in removing toxic chemicals from wastewaters.

AIRS retrieved CO2 and its association with climatic parameters over India during 2004-2011.

Atmospheric Infrared Sounder (AIRS) retrieved mid-tropospheric Carbon Dioxide (CO2) have been used to study the variability and its association with the climatic parameters over India during 2004 to 2011. The study also aims in understanding transport of CO2 from surface to mid-troposphere over India. The annual cycle of mid-tropospheric CO2 shows gradual increase in concentration from January till the month of May at the rate ~0.6 ppm/month. It decreases continuously in summer monsoon (JJAS) at the same rate during which strong westerlies persists over the region. A slight increase is seen during winter monsoon (DJF). Being a greenhouse gas, annual cycle of CO2 show good resemblance with annual cycle of surface air temperature with correlation coefficient (CC) of +0.8. Annual cycle of vertical velocity indicate inverse pattern compared to annual cycle of CO2. High values of mid-tropospheric CO2 correspond to upward wind, while low values of mid-tropospheric CO2 correspond to downward wind. In addition to vertical motion, zonal winds are also contributing towards the transport of CO2 from surface to mid-troposphere. Vegetation as it absorbs CO2 at surface level, show inverse annual cycle to that of annual cycle of CO2 (CC-0.64). Seasonal variation of rainfall-CO2 shows similarities with seasonal variation of NDVI-CO2. However, the use of long period data sets for CO2 at the surface and at the mid-troposphere will be an advantage to confirm these results.

On understanding the land-ocean CO2 contrast over the Bay of Bengal: a case study during 2009 summer monsoon.

Ship-based observations of atmospheric carbon dioxide (CO2) concentration over the Bay of Bengal (BoB) between 17 July 2009 and 17 Aug 2009 offered an excellent opportunity to evaluate the land-ocean contrast of surface CO2 and facilitated its comparison with model simulated CO2 concentrations. Elevated values of CO2 with large variability near the coastal region and relatively low values with correspondingly lower variability over the open ocean suggest that this observed CO2 variability over the ocean essentially captures the differences in terrestrial and oceanic CO2 fluxes. Although the region under investigation is well known for its atmospheric intraseasonal oscillations of Indian summer monsoon during July and August, the limited duration of observations performed from a moving ship in a research cruise, is not able to capture any high-frequency variability of atmospheric CO2 concentrations. But band-passed sea surface temperature and wind anomalies do indicate strong intraseasonal variability over the study region during the observational period. The synoptic data, albeit quite short in duration, thus offer a clear benchmark for abrupt variability of CO2 concentration between land and ocean.

Synthesis and pharmacological evaluation of N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide as cyclooxygenase inhibitors.

A series of novel N-substituted 2-(2-oxo-2H-chromen-4-yloxy)propanamide derivatives were synthesized via converting the readily available 4-hydroxy coumarin to the corresponding ethyl 2-(2-oxo-2H-chromen-4-yloxy)propanoate followed by hydrolysis and then reacting with different substituted amines. The molecular structures of two representative compounds, that is, 3 and 5l were confirmed by single crystal X-ray diffraction study. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. The compound 5i showed balanced selectivity towards COX-2 over COX-1 inhibition and good docking scores when docked into the COX-2 protein.

A coverage evaluation survey of JE vaccination in two districts of Karnataka.

A coverage evaluation survey was conducted in Mandya and Koppal districts of Karnataka state following the Japanese Encephalitis (JE) vaccination campaign. The purposes of the survey were to assess coverage of children in target age group by JE vaccination and to assess adverse events following immunisation against JE, the knowledge of health care providers and community about JE & mass vaccination for JE. The study design consisted of both quantitative and qualitative methods. The quantitative data was used to know the coverage levels for children. The qualitative data collected through interviews of head of the family in the sample households, selected health care workers using a structured pretested questionnaire. The standard cluster sampling method was used for selecting the sample of children to be evaluated. In Mandya district the evaluation showed 92% coverage in the selected sample of 313 children against the reported 83.85%. In Koppal district the evaluation showed 70% coverage, among the selected sample of 251 children, against the reported coverage of 69.8%. The incidence of adverse events was 4% in Mandya sample and 6.37% in Koppal sample. In Mandya district, about 42% of households had knowledge of JE. About 68% of households had prior knowledge of the immunization day. In Koppal district, the survey has revealed that only 19.85% of the heads of household had the knowledge of JE and 48.53% had the knowledge of JE vaccination before the day of vaccination campaign.

Spectrophotometric methods for the determination of letrozole in bulk and pharmaceutical dosage forms.

Ultraviolet (UV), first derivative, second derivative, and AUC-spectrophotometric methods for the determination of letrozole in pharmaceutical formulations have been developed. For UV-spectrophotometry, the standard solutions were measured at 240.0 nm. The linearity ranges were found to be 0.25-20.0 µgml(-1) in methanol and the regression equation was A=1.20×10(-1)C+2.22×10(-2)(r(2)=0.9994). For the first derivative spectrophotometry, the response (dA/dλ) of standard solutions was measured at 224.0 nm. The calibration curve was constructed by plotting dA/dλ values against concentrations 0.25-20.0 µgml(-1), of letrozole. The regression equation of the linear calibration graph was calculated as D(1)=3.89×10(-3)C+1.85×10(-4)(r(2)=0.9987). For the second derivative spectrophotometry, the response (d(2)A/dλ(2)) of standard solutions was measured at 241.0 nm. The calibration curve was constructed by plotting d(2)A/dλ(2) values against concentrations 0.5-20.0 µgml(-1) of letrozole standards in methanol. The regression equation of the linear calibration graph was calculated as D(2)=-1.59×10(-3)C-4.66×10(-4)(r(2)=0.9985). The AUC-spectrophotometric method was based on the calculation of Area under Curve (AUC), for analysis of letrozole in the wavelength range of 235.0-245.0 nm. The calibration curve was constructed by plotting AUC values against concentrations 0.25-20.0 µgml(-1), of letrozole. The regression equation of the linear calibration graph was calculated as AUC=1.132C+0.2153 (r(2)=0.9994). The methods were validated by following the analytical performance parameters suggested by the International Conference on Harmonization (ICH). All validation parameters were within the acceptable range. The developed methods were successfully applied to estimate the amount of letrozole in pharmaceutical formulations.

A novel mutation (F71L) in alphaA-crystallin with defective chaperone-like function associated with age-related cataract.

Age-related cataract (ARC) is a multifactorial disease and the leading cause of blindness worldwide. Genetic predisposition in association with other etiological factors may contribute to ARC. However, gene mutation studies on ARC are scanty. In the present work, we identified a genetic variation (F71L) in the exon-2 of CRYAA (alphaA-crystallin) gene in three unrelated female sporadic cases among 711 ARC patients but not in 265 normal non-cataractous controls by SSCP and RFLP analysis. By comparing human recombinant wild-type and F71L-alphaA-crystallin, we characterized the functional significance of this missense mutation. Chromatography, fluorescence and far- and near-UV CD studies indicated that F71L missense mutation did not significantly affect the apparent molecular mass, secondary and tertiary structures and hydrophobicity of alphaA-crystallin. While the mutant alphaA-crystallin displayed significant (35-90%) loss of chaperone-like activity (CLA) in thermal aggregation of carbonic anhydrase, betaL- and gamma-crystallins, it showed moderate (10-50%) loss in CLA in DTT-induced aggregation of insulin and lysozyme. This is the first report of an alphaA-F71L mutation being associated with ARC and suggests that ARC in individuals carrying this mutation (F71L) might be due to the overall loss of in vivo chaperone activity due to interaction with other environmental factors.

Evidence for the association of synaptotagmin with glutathione S-transferases: implications for a novel function in human breast cancer.

OBJECTIVE: To analyze the pattern of changes in GSTs in cancerous and adjacent non-cancerous tissues obtained from breast cancer patients undergoing surgery. DESIGN AND METHODS: Cytosolic GST purification, assay of GST, protein expression levels, and GST-synaptotagmin association were analyzed using standard biochemical techniques like GSH-affinity purification, spectrophotometry, SDS-PAGE, Western blots, and matrix-assisted laser desorption and ionization-time of flight (MALDI-TOF). RESULTS: GST activity in cancerous tissues (0.26 U/mg protein) was significantly higher (P < 0.05) as compared to those from adjacent non-cancerous tissues (0.14 U/mg protein) of breast cancer patients. Further analysis of GST subunits on SDS-PAGE and Western blots using class-specific GST antibodies revealed significant elevation in GST-pi levels in cancer tissues with no appreciable changes in GST-alpha and GST-mu. Along with the elevation of GST-pi levels, high molecular weight proteins (approximately 70 kDa) cross reacting with GST antibodies were detected only in surgically resected tumor biopsies but not in the non-cancerous tissues adjacent to the tumor. Based on MALDI-TOF analysis, the high molecular weight band was identified as synaptotagmin V bound to GST-M1 with 47% sequence coverage after processing on an MS-FIT search engine. CONCLUSIONS: Our results suggest a novel putative functional role for the GST-synaptotagmin complex in human breast cancers. As this association of GST M1-synaptotagmin was not seen in adjacent non-cancerous tissues, this can be used as a marker for breast cancers.

Deoxypreussomerins from Jatropha curcas: are they also plant metabolites?

Three deoxypreussomerins, palmarumycins CP1, JC1 and JC2, have been isolated from a collection of the stems of Jatropha curcas. The second and third compounds are antibacterial constituents which were characterized from spectral evidence. The X-ray crystallographic structure of palmarumycin JC1 was also studied. Deoxypreussomerins have been obtained here from a plant source in appreciable quantities.