Contemporary progress in the green synthesis of spiro-thiazolidines and their medicinal significance: a review

The development of new strategies for the production of nitrogen and sulfur-containing heterocycles remains an extremely alluring but challenging proposition. Among these heterocyclic compounds, spiro-thiazolidines are a distinct class of heterocyclic motifs with an all-encompassing range of pharmaceutical activities such as anti-histaminic, anti-proliferative, anesthetic, hypnotic, anti-fungal, anti-inflammatory, anti-HIV, anthelmintic, CNS stimulant, and anti-viral potentials. Consequently, investigators have produced these heterocycles through diversified intricate pathways as object structures for medicinal studies. Notwithstanding their innumerable manmade solicitations, there is yet no special periodical on MCRs concerning spiro-thiazolidine via green synthesis. Thus, this in-depth review encompasses the excursion of MCRs to spiro-thiazolidines, including the environment-friendly synthetic approaches, reaction situations, rationale behind the optimal selection of catalyst, scope, anticipated mechanism, and biological activities. In this review, we have focussed on the furthermost current developments in spiro-thiazolidine creation under different conditions, such as ionic liquid-assisted, microwave-assisted, on-water, solid-supported acid-catalyzed, asymmetric, and nanocatalyst-assisted syntheses, developed over the last 8 years. This study details works regarding the total amalgamation of spiro-thiazolidines under N- and S-containing heterocycles. Furthermore, this article summarizes the developments of artificially and pharmaceutically important spiro-thiazolidine candidates.

The development of new strategies for the production of nitrogen and sulfur-containing heterocycles remains an extremely alluring but challenging proposition. Current progress in the various synthetic methods and biological activities are discussed.     

Human immunodeficiency virus type 1 Tat modulates proliferation and differentiation of human neural precursor cells: implication in NeuroAIDS

Human immunodeficiency virus type 1 (HIV-1) and viral proteins affect neuronal survival and neuron-glial cell interactions, which culminate in neurological disorders. HIV-1 infects regions of neurogenesis in human adult and pediatric brain. However, little is known about the effect of HIV-1 or viral proteins on the properties of human neural precursor cells (hNPCs), particularly neurogenesis, hence a detailed investigation on these lines is warranted. Human neural precursor cells were cultured in presence and absence of HIV-1B transactivating protein Tat to investigate if HIV-1 viral protein alters the properties of human neural precursor cells. Cellular and molecular approaches were adopted to study the effect of HIV-1B transactivating protein Tat on proliferation and differentiation potential of human fetal brain-derived NPCs. Cell proliferation assays such as BrdU and Ki67 staining and pathway-specific cDNA and protein arrays were used in the study. Data reveal that HIV-1B Tat protein severely affects proliferation of hNPCs, as evident by lower incorporation of BrdU and Ki67 staining as well as neurosphere assay. HIV-1 Tat substantially attenuated neurogenesis, as evident by the smaller numbers of Tuj-1- and doublecortin-positive cells differentiated from hNPCs, without affecting their viability. These data suggest that HIV-1 Tat alters the properties of human neural precursor cells via attenuation of the cell cycle regulatory unit cyclin D1 and the mitogen-activated protein kinase (MAPK) pathway, particularly extracellular signal-related kinase 1/2 (ERK1/2). The study provides new insights into cellular and molecular mechanisms that may modulate human neural precursor cell properties in HIV/AIDS (acquired immunodeficiency syndrome) individuals. Validation with autopsy brain samples is necessary to further substantiate these important observations.     

Agp2p,the Plasma Membrane Transregulator of Polyamine Uptake,Regulates the Antifungal Activities of the Plant Defensin NaD1 and Other Cationic Peptides

Cationic antifungal peptides (AFPs) act through a variety of mechanisms but share the common feature of interacting with the fungal cell surface. NaD1, a defensin from Nicotiana alata, has potent antifungal activity against a variety of fungi of both hyphal and yeast morphologies. The mechanism of action of NaD1 occurs via three steps: binding to the fungal cell surface, permeabilization of the plasma membrane, and internalization and interaction with intracellular targets to induce fungal cell death. The targets at each of these three stages have yet to be defined. In this study, the screening of a Saccharomyces cerevisiae deletion collection led to the identification of Agp2p as a regulator of the potency of NaD1. Agp2p is a plasma membrane protein that regulates the transport of polyamines and other molecules, many of which carry a positive charge. Cells lacking the agp2 gene were more resistant to NaD1, and this resistance was accompanied by a decreased uptake of defensin. Agp2p senses and regulates the uptake of the polyamine spermidine, and competitive inhibition of the antifungal activity of NaD1 by spermidine was observed in both S. cerevisiae and the plant pathogen Fusarium oxysporum. The resistance of agp2Δ cells to other cationic antifungal peptides and decreased binding of the cationic protein cytochrome c to agp2Δ cells compared to that of wild-type cells have led to a proposed mechanism of resistance whereby the deletion of agp2 leads to an increase in positively charged molecules at the cell surface that repels cationic antifungal peptides.     

Hyperglycemia as An Independent Predictor of Worse Outcome in Non-diabetic Patients Presenting with Acute Ischemic Stroke

Objective  To determine if differences in outcome exist between diabetic and non-diabetic patients who present to the Emergency Department (ED) with acute ischemic stoke (AIS) and elevated blood glucose. Methods  The study population consisted of 447 consecutive patients who presented to the ED with AIS within 24 h of symptom onset and had blood glucose measured on presentation. Hyperglycemia was defined as >130 mg/dl. Outcomes studied included infarct volume, stroke severity (NIH Stroke Scale), functional impairment (modified Rankin Score), and 90-day mortality. Patients with hyperglycemia were then stratified into those with and without a prior history of diabetes mellitus (DM) for the purposes of analysis. Results  Patients with hyperglycemia exhibited significantly greater stroke severity (P = 0.002) and greater functional impairment (P = 0.004) than those with normoglycemia. Patients with hyperglycemia were 2.3 times more likely to be dead at 90 days compared to those with normal glucose (P < 0.001). Stroke severity (P < 0.001) and functional impairment (P < 0.001) were both significantly worse in patients with hyperglycemia and no prior history of DM, when compared to patients with hyperglycemia and previously diagnosed DM. Among the patients without a prior history of DM, patients with hyperglycemia were 3.4 times more likely to die within 90 days (P < 0.001) when compared with patients with normoglycemia. In contrast, the hazard ratio was 1.6 among the patients with DM (P = 0.66). Conclusion  Hyperglycemia on presentation is associated with significantly poorer outcomes following AIS. Patients with hyperglycemia and no prior history of DM have a particularly poor prognosis, worse than that for patients with known diabetes and hyperglycemia. Ethics committee approval: The article is part of the project “Emergency Department Stroke Registry” with the Institutional Review Board approval number 1056-04.     

Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound

PURPOSE: The value of MRI and ultrasound in quantifying hepatic steatosis is assessed and the results compared with those obtained by liver biopsies. METHODS: A total of 38 patients undergoing hepatic biopsy for a variety of liver diseases were recruited for this study. Hepatic fat morphology and severity were assessed visually in each biopsy specimen. Steatosis pattern included macrovesicular, microvesicular, or mixed. The severity of hepatic steatosis was assessed by MRI through chemical shift imaging (n = 38) and by ultrasound through echogenicity (n = 31). RESULTS: MRI had a better correlation than ultrasound for microscopic fat content (r = 0.77, P < 0.001 vs. r = 0.41, P < 0.05). In macrovesicular steatosis, MRI and ultrasound both correlated well with microscopic fat content (r = 0.92, P < 0.001 vs. r = 0.90, P < 0.001). In nonalcoholic fatty liver disease, ultrasound revealed severe steatosis in all instances, but MRI fat content ranged greatly (19%-40%). In diagnoses excluding nonalcoholic fatty liver disease, increasing ultrasound severity did not correspond to advanced MRI fat content. CONCLUSION: Hepatic MRI and ultrasound are both useful in identifying heavy fat accumulation associated with nonalcoholic fatty liver disease. MRI is superior to ultrasound in detecting and quantifying minor degrees of fatty metamorphosis in the liver.