An in silico approach to identify novel and potential Akt1 (protein kinase B-alpha) inhibitors as anticancer drugs.

Akt1 (protein kinase B) has become a major focus of attention due to its significant functionality in a variety of cellular processes and the inhibition of Akt1 could lead to a decrease in tumour growth effectively in cancer cells. In the present work, we discovered a set of novel Akt1 inhibitors by using multiple computational techniques, i.e. pharmacophore-based virtual screening, molecular docking, binding free energy calculations, and ADME properties. A five-point pharmacophore hypothesis was implemented and validated with AADRR38. The obtained R2 and Q2 values are in the acceptable region with the values of 0.90 and 0.64, respectively. The generated pharmacophore model was employed for virtual screening to find out the potential Akt1 inhibitors. Further, the selected hits were subjected to molecular docking, binding free energy analysis, and refined using ADME properties. Also, we designed a series of 6-methoxybenzo[b]oxazole analogues by comprising the structural characteristics of the hits acquired from the database. Molecules D1-D10 were found to have strong binding interactions and higher binding free energy values. In addition, Molecular dynamic simulation was performed to understand the conformational changes of protein-ligand complex.

Alteration in haematological and biochemical parameters of Catla catla exposed to sub-lethal concentration of cypermethrin.

A 60-day experiment was carried out to study the effect of sub-lethal concentration of cypermethrin (1/10th of LC(50)) exposure on haematological and biochemical parameters of the Indian major carp, Catla catla fingerlings. Under exposure, the total erythrocyte count, total leucocyte count, haemoglobin content and haematocrit were decreased. All the studied serum parameters viz. total serum protein, albumin, globulin contents and albumin-globulin ratio were significantly decreased in cypermethrin-exposed fishes. A marked increase was recorded in alanine aminotransferase and aspartate aminotransferase activities in liver, whereas lactate dehydrogenase activity of muscle and acetylcholine esterase activity in brain were inhibited in cypermethrin-exposed fish. The membrane transport enzymes (total adenosine triphosphatase, sodium-potassium adenosine triphosphatase and magnesium adenosine triphosphatase) activities were decreased significantly in the gills of C. catla exposed to sub-lethal concentration of cypermethrin. The present study indicates that sub-lethal exposure of C. catla fingerlings to cypermethrin alters the haematological and biochemical parameters.

Synthesis, stereochemistry and antimicrobial evaluation of t(3)-benzyl-r(2),c(6)-diarylpiperidin-4-one and its derivatives.

In a wide research program toward new and efficient antimicrobial agents, a series of t(3)-benzyl-r(2),c(6)-diarylpiperidin-4-ones (1-7) were synthesised and tested for their in vitro antibacterial and antifungal activities. Also, the structures and their stereochemistry of these synthesised compounds 1-7 were characterized by IR, high resolution (1)H NMR, (13)C NMR and (1)H-(13)C COSY spectra. The analysis of coupling constants of compounds 1-5 reveals that they exist in normal chair conformation with equatorial orientations of all the substituents. The spectra of 6 and 7 reveal the presence of two isomers labeled as E (carbonyl carbon is anti to benzyl group at C-3) and Z (carbonyl carbon is syn to benzyl group at C-3) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values the favoured conformation for the Z- and E-isomers of 6 and 7 was found to be the boat conformations. Their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against Cryptococcus neoformans, Candida 6, Candida 51, Aspergillus niger and Aspergillus flavus were also evaluated.

High Mitochondrial Activity but Incomplete Engagement of the Cyanide-Resistant Alternative Pathway in Guard Cell Protoplasts of Pea.

The respiratory properties of guard cell protoplasts (GCP) were examined in comparison with those of mesophyll protoplasts (MCP) from the same leaves of pea (Pisum sativum L. cv Arkel). The rates of respiratory O2 uptake by GCP were extremely high (280 [mu]mol mg-1 Chl h-1) and were several times greater than those of MCP. On the other hand, the rates of photosynthetic O2 evolution by GCP were similar to those of MCP. Also on the basis of protoplast volume, the respiratory rates of GCP were higher: more than three times those of MCP. The enzymes of the tricarboxylic acid cycle, per unit protein or unit protoplast volume, had a 2- to 5-fold higher activity in GCP than in MCP, indicating an enrichment of mitochondrial activity in GCP relative to that in MCP. Respiratory inhibitors were used to assess the activity of the cytochrome (cyanide-sensitive) and alternative (cyanide-resistant) pathways in GCP and MCP. The inhibition of respiration by KCN or antimycin A was more in GCP than that in MCP. The marked inhibition of respiratory O2 uptake by salicylhydroxamic acid in the presence of KCN showed the presence of the cyanide-resistant pathway in GCP. The activity of the cyanide-resistant electron transport path constituted only one-third of total respiration in GCP but accounted for two-thirds of respiration in MCP. The alternative pathway was not completely engaged in GCP but reached its full capacity in MCP.

Light-enhanced dark respiration in mesophyll protoplasts from leaves of pea.

The respiratory oxygen uptake by mesophyll protoplasts of pea (Pisum sativum cv Arkel) was stimulated up to threefold after 15 minutes of illumination at an intensity of 1250 microeinsteins per square meter per second in the presence of 5 millimolar bicarbonate at 30 degrees C. The extent of light-enhanced dark respiration (LEDR) increased progressively with duration of preillumination. The LEDR exhibited two phases. The initial high rate of respiration decreased in about 10 minutes to a lower steady value similar to that before illumination. The promotion of LEDR by the presence of bicarbonate and inhibition by glyceraldehyde or 3-(3,4-dichlorophenyl)-1,1-dimethylurea suggested that LEDR was dependent on products of photosynthetic carbon assimilation/electron transport. Thus, the photosynthetic products exert a markedly quick influence on dark respiration in mesophyll protoplasts.

Tetrazolium Reduction by Guard Cells in Abaxial Epidermis of Vicia faba: Blue Light Stimulation of a Plasmalemma Redox System.

The stomata in the abaxial epidermis of Vicia faba were examined for the location of redox systems using tetrazolium salts. Three distinct redox systems could be demonstrated: chloroplast, mitochondrial, and plasmalemma. The chloroplast activity required light and NADP. Mitochondrial activity required added NADH and was suppressed by preincubation with KCN. The plasmalemma redox system in guard cells also required NADH, but was insensitive to KCN and was stimulated by blue light. The involvement of an NADH dehydrogenase in the blue light stimulated redox system in guard cells was suggested by the sensitivity to plantanetin, an inhibitor of NADH dehydrogenase. The redox system of mitochondria was the most active followed by that of plasmalemma. The activity of chloroplasts was the least among the three redox systems. The plasmalemma mediated tetrazolium reduction was stimulated by exogenous flavins and suppressed by Kl or phenylacetate, inhibitors of flavin excitation. We therefore conclude that an NADH-dependent, flavin mediated electron transport system, sensitive to blue light, operates in the plasmalemma of guard cells.