Synthesis, Characterization And Cholinesterase Inhibitory Activity Of Novel Piperidone Grafted Spiro Heterocycles

Five new series of new spiro-oxindole-pyrrolizine and pyrrolidine hybrids were synthesized employing facile one-pot three-component reaction of linear or cyclic α-amino acids, isatin and various derivatives of N-acryloyl-bis arylidene piperidin-4- ones dipolarophiles. These reactions afforded new mono-spiroheterocycles and bis-spiroheterocycles by changing the ratio of the starting materials from 1:1:1 to 1:2:2 of dipolarophiles, α-amino acid and isatin. These spiro-cycloadducts were further elucidated using elemental analysis, IR, 1-D and 2-D NMR spectroscopy techniques as well as X-Ray crystallographic data. The newly synthesized compounds were also evaluated for their activity against Alzheimer’s disease using Ellman’s colorimetric assay. In this assay the cholinesterase inhibitory activity of the aforementioned compounds were screened in vitro against acetylcholinesterase enzyme (AChE) from electric eel and butyrylcholinesterase enzyme (BChE) from equine serum, which have the major roles in the manifestation and progression of Alzheimer’s disease

(3E,5E)-3,5-Bis(naphthalen-1-yl­methyl­idene)piperidin-4-one

In the title compound, C27H21NO, the piperidine ring adopts a chair conformation. The mean plane through the piperidine ring makes dihedral angles of 49.27 (5) and 63.07 (5)° with the naphthalene ring systems. In the crystal, mol­ecules are linked into dimers via pairs of inter­molecular C—H⋯O inter­actions, generating ten-membered R 2 2(10) ring motifs. C—H⋯π inter­actions further stabilize the crystal structure

Cholinesterase Enzymes Inhibitors from the Leaves of Rauvolfia Reflexa and Their Molecular Docking Study

molecule

(E)-2-(4-Methylbenzylidene)hydrazinecarboxamide

The title compound, C9H11N3O, was synthesized by the reaction of 4-methyl­benzaldehyde with semicarbazide. The mol­ecule adopts an E configuration about the central C=N double bond and the dihedral angle between the mean planes of the benzene ring and the carboxamide groups is 17.05 (9)°. The hydrazine N atoms are twisted slightly out of the plane of the carboxamide group [C—C—N—N torsion angle = 178.39 (14)°] and an intra­molecular N—H⋯N bond generates an S(5) ring. In the crystal, adjacent mol­ecules are connected via a pair of N—H⋯O hydrogen bonds, generating R 2 2(8) loops, resulting in supra­molecular [001] ribbons

5-[(E)-Benzyl­idene]-2-hy­droxy-8,9-di­phenyl-3,10-diaza­hexa­cyclo­[10.7.1.13,7.02,11.07,11.016,20]henicosa-1(19),12(20),13,15,17-pentaen-6-one

In the title compound, C38H30N2O2, the acenaphthyl­ene ring is close to being planar [maximum deviation = 0.1047 (11) Å]. The dihedral angles between the three benzene rings and the acenaphthyl­ene system are 39.47 (3), 37.65 (3) and 44.47 (3)°. An intra­molecular O—H⋯N inter­action forms an S(5) hydrogen-bond ring motif. In the crystal, mol­ecules are linked into [101] chains by a set of C—H⋯O inter­actions

(3E,5E)-3,5-Dibenzyl­idene-1-[3-(piperidin-1-yl)propano­yl]piperidin-4-one

The asymmetric unit of the title compound, C27H30N2O2, comprises two independent mol­ecules. The dihedral angles between the phenyl rings in the two mol­ecules are 55.59 (8) and 55.39 (8)°. The piperidine rings adopt chair conformations. The crystal structure is stabilized by weak inter­molecular C—H⋯O and C—H⋯N hydrogen bonds. The crystal studied was a non-merohedral twin with a domian ratio of 0.75 (2):0.25 (2)

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years. Methods We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Findings Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2)

Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

How long one lives, how many years of life are spent in good and poor health, and how the population's state of health and leading causes of disability change over time all have implications for policy, planning, and provision of services. We comparatively assessed the patterns and trends of healthy life expectancy (HALE), which quantifies the number of years of life expected to be lived in good health, and the complementary measure of disability-adjusted life-years (DALYs), a composite measure of disease burden capturing both premature mortality and prevalence and severity of ill health, for 359 diseases and injuries for 195 countries and territories over the past 28 years.; We used data for age-specific mortality rates, years of life lost (YLLs) due to premature mortality, and years lived with disability (YLDs) from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 to calculate HALE and DALYs from 1990 to 2017. We calculated HALE using age-specific mortality rates and YLDs per capita for each location, age, sex, and year. We calculated DALYs for 359 causes as the sum of YLLs and YLDs. We assessed how observed HALE and DALYs differed by country and sex from expected trends based on Socio-demographic Index (SDI). We also analysed HALE by decomposing years of life gained into years spent in good health and in poor health, between 1990 and 2017, and extra years lived by females compared with males. Globally, from 1990 to 2017, life expectancy at birth increased by 7·4 years (95% uncertainty interval 7·1-7·8), from 65·6 years (65·3-65·8) in 1990 to 73·0 years (72·7-73·3) in 2017. The increase in years of life varied from 5·1 years (5·0-5·3) in high SDI countries to 12·0 years (11·3-12·8) in low SDI countries. Of the additional years of life expected at birth, 26·3% (20·1-33·1) were expected to be spent in poor health in high SDI countries compared with 11·7% (8·8-15·1) in low-middle SDI countries. HALE at birth increased by 6·3 years (5·9-6·7), from 57·0 years (54·6-59·1) in 1990 to 63·3 years (60·5-65·7) in 2017. The increase varied from 3·8 years (3·4-4·1) in high SDI countries to 10·5 years (9·8-11·2) in low SDI countries. Even larger variations in HALE than these were observed between countries, ranging from 1·0 year (0·4-1·7) in Saint Vincent and the Grenadines (62·4 years [59·9-64·7] in 1990 to 63·5 years [60·9-65·8] in 2017) to 23·7 years (21·9-25·6) in Eritrea (30·7 years [28·9-32·2] in 1990 to 54·4 years [51·5-57·1] in 2017). In most countries, the increase in HALE was smaller than the increase in overall life expectancy, indicating more years lived in poor health. In 180 of 195 countries and territories, females were expected to live longer than males in 2017, with extra years lived varying from 1·4 years (0·6-2·3) in Algeria to 11·9 years (10·9-12·9) in Ukraine. Of the extra years gained, the proportion spent in poor health varied largely across countries, with less than 20% of additional years spent in poor health in Bosnia and Herzegovina, Burundi, and Slovakia, whereas in Bahrain all the extra years were spent in poor health. In 2017, the highest estimate of HALE at birth was in Singapore for both females (75·8 years [72·4-78·7]) and males (72·6 years [69·8-75·0]) and the lowest estimates were in Central African Republic (47·0 years [43·7-50·2] for females and 42·8 years [40·1-45·6] for males). Globally, in 2017, the five leading causes of DALYs were neonatal disorders, ischaemic heart disease, stroke, lower respiratory infections, and chronic obstructive pulmonary disease. Between 1990 and 2017, age-standardised DALY rates decreased by 41·3% (38·8-43·5) for communicable diseases and by 49·8% (47·9-51·6) for neonatal disorders. For non-communicable diseases, global DALYs increased by 40·1% (36·8-43·0), although age-standardised DALY rates decreased by 18·1% (16·0-20·2). With increasing life expectancy in most countries, the question of whether the additional years of life gained are spent in good health or poor health has been increasingly relevant because of the potential policy implications, such as health-care provisions and extending retirement ages. In some locations, a large proportion of those additional years are spent in poor health. Large inequalities in HALE and disease burden exist across countries in different SDI quintiles and between sexes. The burden of disabling conditions has serious implications for health system planning and health-related expenditures. Despite the progress made in reducing the burden of communicable diseases and neonatal disorders in low SDI countries, the speed of this progress could be increased by scaling up proven interventions. The global trends among non-communicable diseases indicate that more effort is needed to maximise HALE, such as risk prevention and attention to upstream determinants of health

Prometheus Home Control System [power line communications]

The Prometheus system from Nexus Technologies will provide users with a practical low cost implementation of a smart home. Our smart home design will allow users to control the lights of their house from either a local computer, or any computer connected to the internet. The building controller determines what device the user intends to control by the data received and sends control signals to the Power Line Communication Modem (PLCM). The control signals are processed by the PLCM and sent through the electrical grid. These control signals are then recovered from the electrical grid by another PLCM located near the corresponding light that is to be controlled

Design, synthesis and cholinesterase inhibitory evaluation study of fluorescent N-benzylpiperidine-4-one derivatives

Some N-benzylpiperidine-4-one derivatives were synthesized via one-pot three-component protocols in excellent yields, and were evaluated for their potential cholinesterase inhibition. The mono-substituted derivatives except 4b showed butyrylcholinesterase selective, while unsubstituted and di-substituted derivatives showed acetylcholinesterase selective inhibitions. It is interesting to note that all the mono-substituted derivatives showing butyrylcholinesterase inhibitory activity were more potent than galanthamine. Compound 4c bearing ortho-methoxy group showed the most potent, mixed-mode inhibitory activity on both acetylcholinesterase and butyrylcholinesterase with IC 5.67 and 0.87 μM, respectively. Molecular docking revealed that compound 4c had hydrophobic interactions and hydrogen bonding at the catalytic triad and choline binding sites of the enzymes. In conclusion, this simple and cheaper synthesis method yielded derivatives with good cholinesterase inhibition and favorable photophysical properties