Design, Synthesis, and Pharmacological Evaluation of Novel Tacrine Derivatives as Multi-target ANTI-Alzheimer's Agents In Rat Models.

BACKGROUND: Alzheimer's disease is a progressive neurodegenerative disorder for which no curative drugs are available and treatment available is just palliative. OBJECTIVES: Current research focused on design of Tacrine-Flavone hybrids as multitargeted cholinesterase and monoamine oxidase B inhibitors. METHODS: A total of 10 Tacrine- Flavone hybrids were designed, synthesized and characterized. The in vitro neurotoxicity and hepatotoxicity of the synthesized compounds determined using SHSY5Y cell line and HEPG2 cell line. One most active compound (AF1) with least toxicity in in vitro studies was chosen for in vivo studies. Acute and subacute toxicity of the novel compound AF1 conducted on Wistar rats according to OECD guideline 423 and 407. The LD50 value of the novel compound calculated according to Finney's method using Probit analysis. Anti-Alzheimer's activity studies conducted on male Wistar rats. Behavioral studies conducted and AChE and MAO-B activity determined in rat brain. RESULTS AND DISCUSSION: All the compounds exhibited good inhibitory effect on MAO B and AChE. The neurotoxicity studies of the active compound AF1 did not show toxicity up to 100µg. The hepatotoxicity study of the most active compound AF1, showed the compound to be safe up to 200µg. The LD 50 value of the novel compound after a single oral administration was found to be 64 mg/kg bodyweight in rats. Subacute toxicity studies did not show any remarkable toxicity in the vital organs up to 40 mg/kg. Activity studies showed comparable results with standard at 20 mg/kg. CONCLUSION: The results showed that the novel Tacrine-Flavone hybrids are multitarget-directed ligands, which are safe and active compared to tacrine and can be a promising lead molecule for further study.

Microwave hydrothermal synthesis of α-MnMoO4 nanorods for high electrochemical performance supercapacitors.

Pristine α-MnMoO4 nanorods were facilely prepared via co-precipitation (Cp) and microwave hydrothermal (MH) methods. X-ray diffraction (XRD) patterns showed pure monoclinic crystalline phase α-MnMoO4 for the heat treated powder at 500 °C. Fourier Transform Infrared (FTIR) spectra showed that the chemical bond structure of α-MnMoO4 corresponds to the strong vibrational modes of Mo-O-Mo, Mo-O and Mo[double bond, length as m-dash]O. Raman spectra showed the structural bonding and crystalline nature of α-MnMoO4. Field Emission Scanning Electron Microscope (FE-SEM) images exposed the nanorod shape of the α-MnMoO4 powder, with diameters of ∼200 nm and lengths of ∼1.6 µm. Electrochemical studies of the Cp- and MH-MnMoO4 nanorods with 2 M NaOH as the electrolyte showed specific capacitances of 143 F g-1 and 551 F g-1, respectively, at a 1 A g-1 constant discharge current density. Cyclic voltammetric (CV) studies of the MH-MnMoO4 nanorods at various scan rates revealed the presence of redox pairs, suggesting a pseudocapacitive nature. The structural stability at different current densities demonstrated the high rate performances and good reversible capacity retention of the calcined MH-MnMoO4 nanorods. A cycling life stability study of MH-MnMoO4 demonstrated a good capacity retention of 89% of the initial specific capacitance at 5 A g-1 after 1000 cycles.

Biosynthesis of silver nanoparticles using dried fruit extract of Ficus carica - Screening for its anticancer activity and toxicity in animal models.

There is an increasing commercial demand for various nanoparticles due to their extensive applicability in various areas such as electronics, catalysis, chemistry, energy and medicine. Metallic nanoparticles are traditionally synthesized by wet chemical techniques, where the chemicals used are quite often toxic and flammable. Fig has been a typical fruit component of the health-promoting Mediterranean diet for a very long time. In the present study, we describe a cost effective and eco-friendly technique for green synthesis of silver nanoparticles from 1 mM AgNO3 solution through the extract of dried fig (Ficus carica L.) fruit as reducing as well as capping agent. Nanoparticles were characterized using UV absorption spectroscopy and SEM. The sizes of the spherical silver particles were found to be in the range of 54-89 nm. The biologically synthesized nanoparticles also exhibited a significant cytotoxic effect on MCF7cell lines and further animal acute toxicity results state that the above AgNPs are toxicologically safe by oral administration.

Ultrathin spinel LiMn2O4 nanowires as high power cathode materials for Li-ion batteries.

Ultrathin LiMn(2)O(4) nanowires with cubic spinel structure were synthesized by using a solvothermal reaction to produce α-MnO(2) nanowire followed by solid-state lithiation. LiMn(2)O(4) nanowires have diameters less than 10 nm and lengths of several micrometers. Galvanostatic battery testing showed that LiMn(2)O(4) nanowires deliver 100 and 78 mAh/g at very high rate (60C and 150C, respectively) in a larger potential window with very good capacity retention and outstanding structural stability. Such performances are due to both the favorable morphology and the high crystallinity of nanowires.

Protective effect of Morinda citrifolia fruits on beta-amyloid (25-35) induced cognitive dysfunction in mice: an experimental and biochemical study.

The neuroprotective effect of an ethyl acetate extract of Morinda citrifolia (Rubiaceae) Linn. fruits (EMC, ethyl acetate extract of Morinda citrifolia) at doses of 200 and 400 mg/kg, p.o. was studied on beta-amyloid (25-35) peptide induced cognitive dysfunction in mice. In the step-down inhibitory avoidance, EMC exhibited a significant increase in short-term memory and long-term memory (p < 0.05). A significant decrease (p < 0.01) in escape latency was noticed in the animals in the water maze. A significant increase (p < 0.01) in alteration of behavior was exhibited upon administration of EMC 200 and 400 mg/kg on the Y maze. Exploratory parameters such as line crossings, head dipping and rearing were increased significantly in EMC treated groups in a dose-dependent manner (p < 0.05 and p < 0.01). A significant reduction (p < 0.05) in acetyl cholinesterase activity was noticed in the EMC 200 and 400 mg/kg treated groups. The level of monoamine oxidase-A was decreased by the administration of EMC 200 and 400 mg/kg (p < 0.05 and p < 0.01, respectively). EMC at a dose of 400 mg/kg exhibited a significant increase (p < 0.01) in the levels of serotonin and dopamine. Antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase and ascorbic acid were decreased significantly in the b-amyloid peptide injected group, whose levels were restored significantly (p < 0.01) by the administration of EMC (400 mg/kg).

Spinel LiMn2O4 nanorods as lithium ion battery cathodes.

Spinel LiMn2O4 is a low-cost, environmentally friendly, and highly abundant material for Li-ion battery cathodes. Here, we report the hydrothermal synthesis of single-crystalline beta-MnO2 nanorods and their chemical conversion into free-standing single-crystalline LiMn2O4 nanorods using a simple solid-state reaction. The LiMn2O4 nanorods have an average diameter of 130 nm and length of 1.2 microm. Galvanostatic battery testing showed that LiMn2O4 nanorods have a high charge storage capacity at high power rates compared with commercially available powders. More than 85% of the initial charge storage capacity was maintained for over 100 cycles. The structural transformation studies showed that the Li ions intercalated into the cubic phase of the LiMn2O4 with a small change of lattice parameter, followed by the coexistence of two nearly identical cubic phases in the potential range of 3.5 to 4.3 V.