Comprehensive review on natural pharmacophore tethered 1,2,3-triazoles as active pharmaceuticals

The privileged 1,2,3-triazole scaffold is drawing researcher's attention due to its widespread applications in diverse fields such as drug discovery (e.g., carboxyamidotriazole), organic synthesis (click-reaction template), polymeric materials (e.g., triazolamer), supramolecular receptors (e.g., triazolophane), fluorescent materials (e.g., metal–organic frameworks), and agricultural sectors (e.g., fungicides). Various 1,2,3-triazole persuasion modules are also currently available in the market that have multiple assets such as active pharmaceuticals and agricultural purposes. Owed to the highly consistent and firmest synthesis approach, that is, click reaction of various azides and acetylene derivatives by copper (I)-catalyzed 1,3-dipolar cycloaddition (CuAAC), highly functionalized 1,2,3-triazoles are prepared in scalar yields for drug discovery. Given the importance of 1,2,3-triazole chemistry, the present review focuses specifically on the synthesis of structurally diverse 1,2,3-triazoles linked to natural pharmacophores and their biological importance. Furthermore, the dual/multi-pharmacophores assimilated 1,2,3-triazoles have listed interesting biological activities that could be valuable as future drug leads. In addition, this comprehensive review can serve as a template for the development of new diverse scaffolds that will ensure for new therapeutic approaches for the existing myriad diseases and disorders.     

Level,Causes and Risk Factors of Neonatal Mortality,in Jordan: Results of a National Prospective Study

Objective The present study aimed at assessment of the magnitude of neonatal mortality in Jordan, and its causes and associated factors. Methods Through a multistage sampling technique, a total of 21,928 deliveries with a gestational period ≥20 weeks from 18 hospitals were included in the study. The status of their babies 28 days after birth, whether dead or alive, was ascertained. Extensive data were collected about mothers and their newborns at admission and after 28 days of birth. Causes of death were classified according to the neonatal and intrauterine death classification according to etiology. Preventability of death was classified according to Herman’s classification into preventable, partially preventable, and not preventable. Results Neonatal mortality rate, overall and for subgroups of the study was obtained. Risk factors for neonatal mortality were first examined in bivariate analyses and finally by multivariate logistic regression models to account for potential confounders. A total of 327 babies ≥20 weeks of gestation died in the neonatal period (14.9/1000 LB). Excluding babies <1000 g and <28 weeks of gestation to be consistent with the WHO and UNICEF’s annual neonatal mortality reports, the NNMR decreased to 10.5/1000 LB. About 79 % of all neonatal deaths occurred in the first week after birth with over 42 % occurring in the first day after birth. According to NICE hierarchical classification, most neonatal deaths were due to congenital anomalies (27.2 %), multiple births (26.0 %), or unexplained immaturity (21.7 %). Other important causes included maternal disease (6.7 %), specific infant conditions (6.4 %), and unexplained asphyxia (4.9 %). According to Herman’s classification, 37 % of neonatal deaths were preventable and 59 % possibly preventable. An experts’ panel determined that 37.3 % of neonatal deaths received optimal medical care while the medical care provided to the rest was less than optimal. After adjusting for socio-demographic characteristics, type of the hospital, and clinical and medical history of women, the following variables were significantly associated with neonatal mortality: male gender, congenital defects, inadequate antenatal visits, multiple pregnancy, presentation at delivery, and gestational age. Conclusion The present study showed the level, causes, and risk factors of NNM in Jordan. It showed also that a large proportion of NNDs are preventable or possibly preventable. Providing optimal intrapartum, and immediate postpartum care is likely to result in avoidance of a large proportion of NNDs.     

Preventive effects of N-acetyl cysteine on lipids, lipoproteins and myocardial infarct size in isoproterenol induced myocardial infarcted rats: an in vivo and in vitro study

The present study evaluated the preventive effects of N-acetyl cysteine in isoproterenol induced myocardial infarcted rats. Rats were pretreated with N-acetyl cysteine (10 mg/kg body weight) daily for a period of 14 days. After pretreatment, rats were injected with isoproterenol (100 mg/kg body weight) at an interval of 24 h for two days to induce myocardial infarction. Isoproterenol induced myocardial infarction was indicated by increased activity of creatine kinase-MB and levels of cardiac troponins in the serum. The weight of heart and the levels of serum and heart cholesterol, triglycerides, free fatty acids were increased in isoproterenol induced myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased high density lipoprotein cholesterol. It enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase and the levels of lipid peroxidation products. Pretreatment with N-acetyl cysteine showed significant preventive effects in all the biochemical parameters studied in myocardial infarcted rats. Also, N-acetyl cysteine reduced myocardial infarct size. Histopathological findings of N-acetyl cysteine pretreated myocardial infarcted heart correlated with these biochemical findings. The in vitro study confirmed the strong antioxidant action of N-acetyl cysteine. Thus, the present study revealed that N-acetyl cysteine prevented increased heart weight, accumulation of lipids, altered levels of lipoproteins thereby reducing myocardial infarct size due to its antilipidemic and antioxidant effects in isoproterenol induced myocardial infarcted rats. This study may have a significant impact on myocardial infarction.     

A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry

A 58 kb region on chromosome 9p21.3 has consistently shown strong association with coronary artery disease (CAD) in multiple genome-wide association studies in populations of European and East Asian ancestry. In this study, we sought to further characterize the role of genetic variants in 9p21.3 in African American individuals. Apparently healthy African American siblings (n = 548) of patients with documented CAD < 60 years of age were genotyped and followed for incident CAD for up to 17 years. Tests of association for 86 single-nucleotide polymorphisms (SNPs) across the 9p21.3 region in a generalized estimating equation logistic framework under an additive model adjusting for traditional risk factors, family, follow-up time and population stratification were performed. A single SNP within the CDKN2B gene met stringent criteria for statistical significance, including permutation-based evaluations. This variant, rs3217989, was common (minor allele (G) frequency 0.242), conveyed protection against CAD (odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.07 to 0.50, P = 0.0008) and was replicated in a combined analysis of two additional case/control studies of prevalent CAD/MI in African Americans (n = 990, P = 0.024, OR = 0.779, 95% CI: 0.626-0.968). This is the first report of a CAD association signal in a population of African ancestry with a common variant within the CDKN2B gene, independent from previous findings in European and East Asian ancestry populations. The findings demonstrate a significant protective effect against incident CAD in African American siblings of persons with premature CAD, with replication in a combination of two additional African American cohorts.