Eaton’s reagent catalysed alacritous synthesis of 3-benzazepinones

An expeditious method for the synthesis of 3-benzazepinones has been developed by using a mixture of phosphorus pentoxide-methane sulfonic acid (Eaton’s reagent) at room temperature under solvent and metal catalyst free condition. Wide functional group tolerance, mild reaction conditions, simple procedure, ease of work-up and high yields is the citable features of this protocol

Purification and biochemical characterization of a novel secretory dipeptidyl peptidase IV from porcine serum

Purification of DPP-IV enzyme from porcine serum, is presented in this study for the first time. The high molecular weight DPP-IV from porcine serum was fractioned using Sephadex G-75 gel filtration followed by DEAE Sephadex anion exchange and Sephadex G-100 gel filtration chromatography columns with a final yield of 11.25%. The SDS-PAGE of the purified sample showed a single band of molecular mass nearing 160 kDa. Distinct single band was observed after PAS staining confirmed it to be a glycoprotein. The purified enzyme showed an optimum pH and temperature of 8 and 37 degrees C, respectively. The enzyme effectively cleaved fluorogenic substrate Gly-Pro-AMC with Km and Vmax of 4.578 mu M and 90.84 nmoles/min, respectively. Purified DPP-IV activity was inhibited by Diprotin A with an IC(50)value of 8.473 mu M. Among the three plant extracts used to study DPP-IV inhibition, the aqueous hot extract ofTerminalia chebulashowed the highest inhibition of 87.19%, followed by the aqueous cold extract ofMomordica carantia, ( 31.6%) andAzadirachta indica(34.16%) at the concentration of 25 mu g

Serine protease from Indian Cobra venom: its anticoagulant property and effect on human fibrinogen

An unusual low molecular weight serine protease (NnP28) has been purified from Indian Cobra (Naja naja) venom from the western region of the Indian sub-continent. We reported the purification and characterization of low molecular NnP28, emphasizing its role on human fibrinogen and anticoagulant property. NnP28 was purified using gel filtration column chromatography followed by ion exchange chromatography. Protein gel electrophoresis revealed its molecular weight approximate to 28 kDa. The exact molecular mass of NnP28 was found to be 27.12 kDa by mass spectrometry, hydrolyzing casein specifically, inhibited by PMSF suggesting it has a serine protease. NnP28 prolonged the clotting time of re-calcified human citrated plasma and activated partial thromboplastin time (APTT) exhibiting anticoagulant property. NnP28 exhibited fibrinogenolytic activity. Thus, the present study demonstrates the presence of unusual low molecular weight serine protease, emphasizing its importance of region-specific Indian cobra species

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

A mild and efficient method for the deprotection of trimethyl silyl alkynes using sodium ascorbate and copper sulphate

A competent and fast method for the deprotection of trimethyl silyl group was attained by using cheap, easily accessible, and nontoxic sodium ascorbate in combination with copper sulphate. The method labored was simple and effective for the cleavage of trimethyl silyl group from the protected trimethyl silyl alkynes to their corresponding alkyne derivatives. Wide functional group tolerance, shorter time period, simple procedure and high yields are the striking features of this protocol

Novel synthesis of N-unsubstituted imidazoles via the cycloaddition of N-(tert-butylsulfinyl)imines and TosMIC

A facile and efficient method was developed for the synthesis of N-unsubstituted imidazoles via the cycloaddition of N-sulfinyl imines and p-toluenesulfonylmethyl isocyanide (TosMIC). This methodology is operationally simple and useful for the preparation of various aromatic and heteroaromatic imidazoles in good to excellent yields. (C) 2020 Published by Elsevier Ltd

A novel and expeditious synthesis of oxazolidinone drugs linezolid and eperezolid

A concise and efficient synthesis of linezolid and eperezolid were accomplished through a convergent scheme utilizing diverse reaction conditions. The synthesis demonstrates utility of a new approach to facilitate the expeditious construction of 3-aryl-5-(substituted methyl)-2-oxazolidinones and easier insertion of N-acetyl group. This new approach offers the possibility of accessing related 2-oxazolidinone members easily as well as making additional analogues of Linezolid. The adopted method afforded high purity and excellent yield compared to other existing synthetic methods. The compounds were successfully characterized by known spectroscopic techniques

1,8-Diazabicyclo5.4.0]undec-7-ene-mediated formation of N-sulfinyl imines

A facile and efficient method was developed for the preparation of a variety of aryl, heteroaryl, and alkyl N-sulfinyl imines using 1,8-diazabicyclo5.4.0]undec-7-ene. In addition to tert-butanesulfinamide, the condensation is also effective with p-toluenesulfinamide. The reaction was performed at room temperature and produces the corresponding N-sulfinyl imines in excellent yields in the absence of acids, metals, and additives. This methodology is also useful for the preparation of N-sulfinyl imines on gram scale. A one-pot synthesis was developed using aryl and heteroaryl alcohols with both tert-butanesulfinamide and p-toluenesulfinamide at room temperature, resulting in the corresponding N-sulfinyl imines with good yields

Zinc chloride catalyzed, dipolar aprotic solvent-mediated, one-pot synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols

A three-component one-pot method has been developed for the synthesis of 2-[(benzo[d]thiazol-2-ylamino)(phenyl)methyl]phenols from a variety of aldehydes, 2-amino-1,3-benzothiazoles, and phenols. Phenol, substituted phenols, and polyhydroxybenzenes participated well, providing the corresponding derivatives in good yields. In the case of polyhydroxybenzenes, for which the formation of positional isomers or dimers might have been possible, the sterically less hindered positional isomer was formed exclusively via the ortho-quinone methide