Sunil Kumar Rai

PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment

Zollo et al. report that mutations in PRUNE1, a phosphoesterase superfamily molecule, underlie primary microcephaly and profound global developmental delay in four unrelated families from Oman, India, Iran and Italy. The study highlights a potential role for prune during microtubule polymerization, suggesting that prune syndrome may be a tubulinopathy.

Unusual reverse face-to-face stacking in propylene linked pyrazole system: perspective of organic materials

Flexible dimers 1, 2, and 3 of “pyrazole” derivatives linked with propylene spacer are synthesized and conformational stability in solid, solution, and gaseous states is studied through single crystal X-ray diffraction, 2D NOESY ,and DFT, respectively. The folded conformation of compound 2 is stable in all three states and X-ray diffraction evince that molecule is intramolecularly stacked in reverse face-to-face manner. TEM image of compound 2 exhibits rigid hollow nanospikes with high tendency to form agglomerates.

Cascade synthesis of 2-pyridones using acrylamides and ketones

Microwave assisted non-catalytic condensation of 2-cyanoacetamide with aromatic aldehydes, and enolate mediated Michael-type addition to acrylamide followed by oxidative cyclization, produce 2-pyridones in good to excellent yield. Unsymmetrical ketones produce two regioisomeric enolates, therefore thermodynamic and kinetic products of butan-2-one and pentan-2-one have been isolated and fully characterized.

Face-to-face stacking in sulfonamide based bis-ethylene bridged heteroaromatic dimers

Four sulfonamide based bis-ethylene bridged heteroaromatic dimers were synthesized for analysis of their structural and conformational properties. Interestingly, all models showed intramolecular offset face-to-face stacking between the tosyl group and heteroaromatic system in their solid state conformations. 1H NMR of the solutions revealed that the conformations were not far off from the solid state stacked geometry. However, gaseous state optimizations of different conformers divulged that the crystal structures were the lowest energy conformers.

Epidemiology of Congenital Heart Disease in India

OBJECTIVE Congenital heart defects (CHDs) affect a large number of newborns and account for a high proportion of infant mortality worldwide. There are regional differences in the prevalence and distribution pattern of CHDs. The aim of this study is to estimate the distribution pattern and prevalence of CHDs among the population of north-central India and to compare the results with studies in other regions of the country to get an overview of prevalence of CHDs in India. DESIGN We carried out a prospective study in the outpatient department of a tertiary care referral center in north-central India. This study was carried out from January 2011 to April 2014, with 34 517 individuals being recruited for the study. All patients were examined by chest x-ray, electrocardiogram, and 2D echocardiography. Prevalence rate per 1000 individuals examined was calculated. Relative frequencies of individual CHD types as a proportion of total CHDs were also calculated. RESULTS Out of 34 517 individuals examined, 661 were diagnosed with CHDs, giving a prevalence of 19.14 per 1000 individuals. The most common defect was ventricular septal defect (33%), followed by atrial septal defect (19%) and tetralogy of Fallot (16%). The majority of CHD cases (58%) diagnosed were between 0 and 5 years of age. The prevalence of CHDs in adults was 2.4 per 1000 individuals in this cohort, with atrial septal defect (44.5%) being the most frequent defect. CONCLUSION The prevalence of CHDs in our cohort was high, possibly because of the power of the diagnostic methods we used and the inclusion of all age groups. Adults with CHDs may significantly contribute to the prevalence of CHDs in the next generation, and this needs to be considered when estimating prevalence rates. Although several small regional studies have been carried out in India, there is an urgent need to establish a nationwide registry/database for congenital heart defects.

Polymorphic study and anti-inflammatory activity of a 3-cyano-2-pyridone based flexible model

This work deals with the synthesis, crystallization and the polymorphic interpretation of 2-{3-[3-cyano-6-methyl-2-oxo-4-phenylpyridin-1(2H)-yl]propoxy}-4-methyl-6-phenylnicotinonitrile (2). The quantitative analysis of the two polymorphs has been achieved through single crystal X-ray diffraction and Hirshfeld surface analysis. However, differential scanning calorimetry has been performed to determine the thermal stability and density functional theory to interpret the conformation on the propylene linker. Furthermore, the binding affinity of compound 2 was evaluated through a docking study in the COX-2 active site. An in vivo study revealed significant anti-inflammatory activity. Moreover, solubility of both polymorphs was checked in a 50% MeOH–water mixture and phosphate buffer (pH = 7.40).

A prospective pilot study on serum cleaved tau protein as a neurological marker in severe traumatic brain injury

Abstract Objective: Neurotrauma has been labelled as a “silent epidemic” affecting both the developed and the developing nations. To date, no single brain-specific biomarker has been unanimously accepted for routine clinical use in TBI. Our study aims to determine the correlation of “cleaved-tau protein” in severe traumatic brain injury (TBI) with Glasgow Coma Scale (GCS) at the time of admission, mode of injury, CT findings and outcome at discharge. Methods: The study has been approved by the institutional ethical committee. 40 cases with severe TBI and 40 randomly selected healthy controls were included in this prospective study. Venous blood samples were collected and serum cleaved tau protein levels were measured and correlated with gender, mode of injury, CT findings GCS score and GOS score at discharge. Results: In the severe TBI group, the mean serum cleaved tau protein levels in males were 91.65 ± 41.34 pg/ml (mean ± S.D.), and females were 104.43 ± 53.08 pg/ml (mean ± S.D.), (p = 0.27). Mean serum C-tau level in study group was 95.48 ± 44.87 pg/ml (range 36.44-192.34), 95% C.I. (81.13–109.83) and in controls was 33.82 ± 13.65 pg/ml (range 2.48–66.54), 95% C.I. (29.46–38.19) (p < 0.001). The distribution of serum C-tau was in severe TBI group varied in all categories of GCS at 0th day (p < 0.001). Serum cleaved tau protein levels in the good outcome group were 74.26 ± 25.43 pg/ml (mean ± S.D.), range 36.44–144.54, 95% C.I. (63.52-85.00) and the poor-outcome group were 127.32 ± 49.40 pg/ml, range 66.65–192.34, 95% C.I. (100.99-153.64) (p = 0.001). Conclusion: In severe TBI, serum cleaved tau protein levels were significantly higher as compared to the controls in this prospective study. However, results of this study are preliminary in nature and there is a need to undertake larger prospective studies to reach a definitive conclusion.

An efficient and controlled synthesis of persulfonylated G1 dendrimers via click reaction

This work presents the first report, we believe, on controlled synthesis of clickable dendrimers using aromatic and heteroaromatic cores and persulfonylated dendrons. Owing to poor thermal stability of persulfonylated dendrons, CuAAC reaction conditions were standardized at room temperature. Click reactions went smoothly with Cu(PPh3)3Br complex in the presence of tridentate chelating ligands and produced copper-free G1 dendrimers in excellent yield. This methodology has now unveiled the peripheral decoration of high generation POPAM dendrimers with persulfonyl groups in a one-step click reaction.

Dual role of drugs: beneficial and harmful aspects

Abstract Drugs are the compounds used for treatment of diseases; but when found having side-effects such as addiction, there starts their harmful effects on the body, the phenomenon of what is called drug abuse. This chapter is confined to those drugs that were isolated from natural resources or being derived from them, and have their medical applications as well as abuse. We have described from their historical background the chemical and biosyntheses. Herein, we have reviewed amphetamine, charas, cocaine, heroin, and lysergic acid diethylamide in detail.