<Emphasis Type="Italic">In silico</Emphasis> modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of β-amyloid plaques associated with Alzheimer's disease

Background  

Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by β-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of β-amyloid plaques.     

Cyclin-dependent kinase TPK2 is a critical cell cycle regulator in Toxoplasma gondii

The Apicomplexan parasite Toxoplasma gondii replicates by endodyogeny, an unusual form of binary fission. We tested the role of TPK2, a homologue of the CDC2 cyclin-dependent kinases, in cell cycle regulation. TPK2 tagged with HA epitope (TPK2-HA-wt) was expressed in mammalian cells as confirmed by Western blot analysis using HA tag and PSTAIRE antibodies. TPK2-HA-wt phosphorylated a peptide from Histone H1, proving that TPK2 is a functional kinase. TPK2-HA-wt coimmunoprecipitated with mammalian cyclins A, B1, D3 and E. Despite being a functional kinase, TPK2 did not rescue Schizosaccharomyces pombe cdc2 and Saccharomyces cerevisiae cdc28 mutant strains. Overexpression of a dominant-negative mutant of TPK2 (TPK2-HA-dn) in T. gondii tachyzoites arrested replication. FACS analysis of tachyzoites expressing TPK2-HA-dn revealed an increase in the fraction of cells in S-phase when compared with TPK2-HA-wt transfected parasites. Expression of TPK2-HA-wt did not arrest tachyzoite replication. No discernable G2 cell cycle block was evident suggesting that cell cycle checkpoints differ in T. gondii from most other eukaryotic cells. These data suggest that TPK2 executes an essential function in T. gondii cell cycle and is likely to be the T. gondii CDC2 orthologue.     

Effect of age of seedling and phytohormones on micropropagation of indica rice (Oryza sativa L.) from Meristem Culture.

An efficient protocol forin vitro micropropagation of seven indica rice varieties was developed from meristem culture. Meristem (leaf base) was isolated from different age of seedlings and cultured on MS medium without hormones and supplemented with different concentrations of NAA and BAP. Regeneration of plantlets from meristem was observed within five days of culture. The meristem isolated from 4-day old seedlings gave highest regeneration on hormone free MS medium. Histological study of meristem (leaf base) from 4-day old seedlings confirmed the presence of meristematic cells. Regenerated plants were multiplied on MS medium supplemented with 0.05 mg/L NAA and 5 mg/L BAP. An average of five plants were obtained from single regenerated meristem. The plants regenerated from meristem showed morphological uniformity.     

Epimers from the leaves of Calophyllum inophyllum

The ethanolic extract of the fresh leaves of Calophyllum inophyllum afforded a pair of new epimers named as inophynone and isoinophynone. Their structures were elucidated with the aid of spectroscopic techniques. Some known constituents, cholesterol, friedelin, canophyllol and canophyllic acid, were also isolated from the same source.     

Development of an immunosensor for the detection of vitellogenin using impedance spectroscopy

A simple and direct immunosensor for the determination of carp (Carassius auratus) vitellogenin (Vtg), a female-specific protein, has been proposed based on an antibody-captured conducting polymer-coated electrode. The monoclonal antibody specific to carp (C. auratus) Vtg was immobilized by covalent coupling to the carboxylic acid group on the polymer. The antibody immobilization and antibody-antigen interaction have been demonstrated by means of quartz crystal microbalance and impedance spectroscopic techniques. The impedance change occurred at the sensor surface due to the specific immuno-interaction was utilized to determine Vtg. The sensor showed high selectivity and sensitive response to Vtg in a buffered medium without redox probe. Vtg was determined in the linear range from 1.0 to 8.0 microg/l with the standard deviation of +/-0.13 (n =3) and the detection limit was determined to be 0.42 microg/l. This method was applied to the determination of Vtg in real male and female carp (C. auratus) serum samples.     

Repeated administration of lead decreases brain 5-HT metabolism and produces memory deficits in rats

Long-term exposure to low levels of lead (Pb2+) has been shown to produce learning and memory deficits in rodents and humans. These deficits are thought to be associated with altered brain monoamine neurotransmission. Increased brain 5-HT (5-hydroxytryptamine; serotonin) activity is thought to be a prerequisite for maintaining control over the cognitive information process, and is said to have a role in learning and memory. This study was designed to investigate the effects of Pb2+ administration on brain 5-HT metabolism and memory function in rats. Rats were injected daily for three weeks with Pb2+-acetate at a dose of 100 mg/kg body weight. The assessment of memory was done using the Radial arm maze (RAM) and Passive avoidance tests. The results showed spatial working memory (SWM) deficits as well as decreased brain 5-HT metabolism. Increased serotonin activity is considered to be an indication of improved cognitive performance. The results are discussed in the context of lead-induced decreases in 5-HT metabolism playing a role in the impairment of memory.     

Xanthones inhibitors of α-glucosidase and glycation from Garcinia nobilis

One new xanthone, caroxanthone (1) together with six known xanthones, 4-prenyl-2-(3,7-dimethyl-2,6-octadienyl)-1,3,5,8-tetrahydroxyxanthone (2), smeathxanthone A (3), gartanin (4), euxanthone (5), 8-hydroxycudraxanthone G (6) and morusignin I (7) were isolated from the stem bark of Garcinia nobilis. The structures were determined by 1D- and 2D-NMR techniques. All these compounds were tested for anti-glycation, α-glucosidase and α-chymotrypsin activities. Some of them exhibited strong to moderate α-glucosidase activities, while none of them inhibited α-chymotrypsin. Compounds 6 and 7 were found to be modest α-glucosidase inhibitors with IC₅₀ values of 76 μM and 84 μM, respectively.     

Inhibition of monoamine oxidase–A activity in rat brain by synthetic hydrazines: Structure-activity relationship (SAR)

A series of hydrazine derivatives was synthesized in order to evaluate their monoamine oxidase A (MAO-A) inhibitory effects. MAO-A inhibitory activity of 4-tosyl benzoic acid carbohydrazide was quite potent, similarly to that of the corresponding 4-benzyloxy-benzoic acid carbohydrazide and its N-cyanoethylated derivative. Structural variations of these compounds, such as the replacement of the 4-substitutent, of the aromatic ring on which the carbohydrazide moiety is grafted, as well as cyclization of the hydrazide moiety in five- or six-membered rings caused either significant decline or complete loss of MAO inhibitory properties. The most active compound (4-tosyl benzoic acid carbohydrazide) was also subjected to the forced swim test, an animal model of depression, eliciting a marked reduction in immobility time in rats, without affecting the locomotor activity, implying that it possesses anti-depressant properties due to inhibition of MAO type-A.     

Seed Priming with Sodium Nitroprusside and H2O2 Confers Better Yield in Wheat Under Salinity: Water Relations,Antioxidative Defense Mechanism and Ion Homeostasis

Journal of Plant Growth Regulation - To mitigate the deleterious effects of abiotic stresses signaling molecules play a significant role. The present study was aimed to assess the responses of two...