THOUGHT OF THE DAY

EDITOR’S CHOICE – Role of Chirality in Drugs

Journal: Infectious Disorders – Drug Targets

Author(s): Hourieh Alkadi*, Rajwa Jbeily

Graphical Abstract:

 

Abstract:

Stereochemistry has occupied a great role in the manufacture and development of pharmaceuticals. Chiral properties play an important role in the determination of pharmacological actions of the drug. In recent years, there is a considerable interest in chiral separation to isolate and examine both enantiomers. This article provides an overview about the stereochemistry and its role in drugs, and also, offers approved isolation methods for enantiomeric pairs.

Read more here: http://www.eurekaselect.com/151186/article

 

New Issue ::: Current Drug Delivery Volume 15, Issue 5

Current Drug Delivery aims to publish peer-reviewed articles, research articles, short and in-depth reviews, and drug clinical trials studies in the rapidly developing field of drug delivery. Modern drug research aims to build delivery properties of a drug at the design phase, however in many cases this idea cannot be met and the development of delivery systems becomes as important as the development of the drugs themselves.

The journal aims to cover the latest outstanding developments in drug and vaccine delivery employing physical, physico-chemical and chemical methods. The drugs include a wide range of bioactive compounds from simple pharmaceuticals to peptides, proteins, nucleotides, nucleosides and sugars. The journal will also report progress in the fields of transport routes and mechanisms including efflux proteins and multi-drug resistance.

The journal is essential for all pharmaceutical scientists involved in drug design, development and delivery.

Articles from the journal Current Drug Delivery Volume 15, Issue 5:

• Delivery of Peptidic Gonadotropin Releasing Hormone Antagonists
• State of the Art of Dental Adhesive Systems
• Carbon Nanotubes: Classification, Method of Preparation and Pharmaceutical Application
• Pulmonary Delivery of Triptorelin Loaded in Pluronic Based Nanomicelles in Rat Model
• Preclinical Assessment of Steroidal Nanostructured Lipid Carriers Based Gels for Atopic Dermatitis: Optimization and Product Development
• Influence of Divalent Cation on Morphology and Drug Delivery Efficiency of Mixed Polymer Nanoparticles
• Design and Evaluation of Transdermal Patches of Timolol Maleate
• Minocycline-loaded In situ Hydrogel for Periodontitis Treatment
• Preparation and Characterization of Stable Nanosuspension for Dissolution Rate Enhancement of Furosemide: A Quality by Design (QbD) Approach
• Rheological Characteristics of Novel Meloxicam-Loaded Complex Organogels Based on Fumed Silica and Poloxamer
• Antiviral Effects of Saffron and its Major Ingredients
• Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets
• Dual-purpose Injectable Doxorubicin Conjugated Alginate Gel Containing Polycaprolactone Microparticles for Anti-Cancer and Anti-Inflammatory Therapy
• Physicochemical and Toxic Properties of Novel Genipin Drug Delivery Systems Prepared by Mechanochemistry
• Influence of Implants Composition on Melatonin Release from Ethylcellulose Matrix

For details on the articles, please visit this link :: https://bit.ly/2IpgeSv

 

WISHING A VERY HAPPY BIRTHDAY DR. MICHAEL KAHN!

DR. MICHAEL KAHN

EDITOR-IN-CHIEF: CURRENT MOLECULAR PHARMACOLOGY

UNIVERSITY OF SOUTHERN CALIFORNIA
1450 BIGGY STREET
LOS ANGELES, NRT 4501, CA 90033
USA

New Issue ::: Current Organic Chemistry 22, Issue 6

Current Organic Chemistry aims to provide in-depth reviews on the current progress in the fields of bioorganic chemistry, organo-metallic chemistry, asymmetric synthesis, heterocyclic chemistry, natural product chemistry, catalytic and green chemistry, suitable aspects of medicinal chemistry and polymer chemistry, as well as analytical methods in organic chemistry. The frontier reviews provide the current state of knowledge in these fields and are written by chosen experts who are internationally known for their eminent research contributions. The Journal also accepts high quality research papers focusing on hot topics, highlights and letters besides thematic issues in these fields. Current Organic Chemistry should prove to be of great interest to organic chemists in academia and industry, who wish to keep abreast with recent developments in key fields of organic chemistry.

Articles from the journal Current Organic Chemistry Volume 22, Issue 6:

• Knoevenagel Condensation Reactions of Cyano Malononitrile-Derivatives Under Microwave Radiation
• An Overview of the Applications of Ionic Liquids as Catalysts and Additives in Organic Chemical Reactions
• Recent Advances in Organocatalyzed Asymmetric Hydrosilylations
• Applications of Ammonium Bifluoride in Organic Synthesis
• Dendritic Self-Host Phosphorescent Iridium Materials for High-Efficiency Organic Light-Emitting Diodes
• Synthesis and Biomedical Applications of Dendrimers
• Amidoselenation of Alkenes Yielding the β-Amido-selenides through a Radical Pathway

For details on the articles, please visit this link :: https://bit.ly/2KtIEY2

RECENTLY PUBLISHED ISSUES – BENTHAM SCIENCE JOURNALS

Current Protein & Peptide Science 19-7

https://bit.ly/2rUf9XR

Medicinal Chemistry 14-4

https://bit.ly/2IraiUT

Current Topics in Medicinal Chemistry 18-3

https://bit.ly/2IrzD55

Current Pharmaceutical Design 24-8

https://bit.ly/2rQo2RQ

Current Pharmaceutical Design 24-7

https://bit.ly/2rJN1q6

Recent Patents on Computer Science 10-3

https://bit.ly/2rOiRlE

EDITOR’S CHOICE – Association between Apolipoproteins AI and B and Ultrasound Indicators of Carotid Atherosclerosis

Journal: Current Vascular Pharmacology

Author(s): Zeljko Zivanovic*, Ivana Divjak, Mirjana Jovicevic, Tamara Rabi-Zikic, Biljana Radovanovic,Svetlana Ruzicka-Kaloci, Djordje Popovic, Edita Stokic, Ksenija Gebauer-Bukurov, Katarina Zivanovic-Vujcic,Petar Slankamenac

Graphical Abstract:

 

Abstract:

Background: Apolipoproteins A-I and B (apoA-I and apoB) may be better indicators of the risk of cardiovascular and cerebrovascular diseases than conventional risk factors (RFs). The onset of ischemic stroke (IS) may be preceded by the development of atherosclerotic changes in carotid arteries, which can be detected by ultrasound. Only a certain % of patients with IS have an (underlying) carotid etiology.

Objective: The aim of our study was to determine the association between ultrasound indicators of carotid atherosclerosis and the presence of apolipoproteins and other biomarkers in patients with IS.

Methods: The study included 120 patients with clinically first, non-cardioembolic ischemic stroke in the carotid circulation. For all patients the following data were recorded: risk factors (hypertension, diabetes, hyperlipoproteinemia, smoking, obesity, metabolic syndrome, (MetS) hyperhomocysteinemia and inflammation), and levels of blood pressure, glucose, glycosylated hemoglobin, lipids, apoA-I and apoB apolipoproteins, body mass index, homocysteine, and C-reactive protein (CRP). Carotid duplex ultrasound was used to measure carotid intima media thickness (cIMT) and determine the presence of an unstable (hypoechogenic) plaque.

Results: The most significant associations were found between cIMT and older age (β=0.230; p=0.006), lower concentrations of apoA-I (β=-0.244; p=0.008) and a higher apoB/apoA-I ratio (β=0.247; p=0.007). The presence of a hypoechogenic plaque was most significantly associated with increased concentrations of apoB (OR=2.29; 95% CI=4.9-173.5; p<0.0001), the presence of MetS (OR=9.2; 95% CI=2.9-29.2; p<0.0001) and elevated CRP (OR=2.7; 95% CI=1.1-6.9; p = 0.046).

Conclusion: Among RFs and their biomarkers, apoA-I, apoB and the apoB/apoA-I ratio showed strong association with ultrasound indicators of carotid atherosclerosis in IS patients.

Read more here: http://www.eurekaselect.com/156319/article

 

THOUGHT OF THE DAY

PRESS RELEASE – Gene transfer alters the neurodegenerative course of GM2 gangliosidosis

The article by Dr. María Begona Cachon-Gonzalez et al. is published in Current Gene Therapy, Volume 18, 2018

Since its clinical description in 1881, Tay-Sachs disease has had almost totemic significance as a cruel and relentless genetic condition that destroys the developing brain of babies and young children. Formerly considered to be restricted to Ashkenazy Jews, it can occur at almost any age and in any ethnic group. Moreover, with its close relatives, Sandhoff disease and the exceptionally rare GM2 activator deficiency, Tay-Sachs often masquerades as other neurological illnesses. There is no treatment beyond palliative care, and with a pressing medical need so typical of countless other nervous diseases, there is a pressing need and a formidable challenge in contemporary research.

This article considers the history, social context and scientific complexities of Tay-Sachs disease: not only does it represent a metabolic defect of glycosphingolipids but it is, par excellence, a lysosomal disease and so a tantalising target for treatment by functional complementation. Lysosomes were discovered by Christian de Duve; but even though he had had training as a physician, the founding father of Cell Biology had little time for studying the pathogenesis of inborn lysosomal diseases. However, de Duve realised that lysosomes could be readily accessed from outside the cell and, at the end of his life, stated that his research had been motivated by his wish to cure diseases such as Tay-Sachs disease, which progressively destroys nerve cells. In considering Tay-Sachs and related lysosomal diseases, after a prolonged period of therapeutic research, gene therapy at last offers a highly promising and tractable stratagem. This sanguine conclusion emphasises the accuracy of de Duve’s insights and the striking boldness of his vision.

The GM2 gangliosidoses comprise Tay-Sachs and Sandhoff disease as well as the ultra-rare GM2 activator protein deficiency, intimately linked biochemically, pathologically and clinically. Their manifestations result from defects in one of three genes: HEXA, HEXB and GM2A, which code for the α- and β-subunits of β-hexosaminidase and GM2 activator protein, respectively. The integrity of this triad, which cooperate to hydrolyse ganglioside GM2 in the lysosome, is an absolute requirement; and when one or other of the genes is dysfunctional, GM2 ganglioside accumulates progressively in tissues rich in this sphingolipid such as the brain. Disease onset correlates roughly with residual enzymatic activity. Typically, in the acute infantile form arrest of neurodevelopment followed by regression of attained milestones progress inexorably, with death occurring at around 3 years of age, whereas in late-onset forms variable presentations occur that often resemble better-known neurodegenerative conditions.

Since first descriptions of GM2 gangliosidosis in the late nineteenth century as unique and devastating disease entities principally of young children, attempts to eradicate the disease through prevention in at-risk populations has been rapid and highly successful, once the biochemical defects were understood. A testament of this success is demonstrated by the fact that disease prevalence is currently higher in the general population, largely due to a lack of widespread screening programmes.

In common with other lysosomal enzymes, those responsible for the most frequent forms of GM2 gangliosidosis, β-hexosaminidase A and B, are made in the endoplasmic reticulum and travel to the lysosome where they execute their function. However, it was discovered that a significant proportion of these enzymes is secreted into the extracellular space; remarkably, they can be re-captured by neighbouring cells and transported to the lysosome where they function normally – a property that can be exploited in therapeutic applications. Purified enzyme has been injected intravenously and into the cerebrospinal fluid of patients with disappointing results. Substrate reduction therapies to ameliorate the burden of the stored material and pharmacological chaperones have also failed to rescue the disease. This has been attributed principally to the low penetrance of these substances into the brain parenchyma due to the blood-brain-barrier.

The discovery of naturally occurring animal models of disease – several breeds of cat and sheep – together with the creation of mouse strains by genetic manipulation allows systematic evaluation of potential treatments. Gene therapy currently rates as number one stratagem to definitively impact the course of the disease. Impressive outcomes in the mouse model have now been replicated in the larger and more complex cat and sheep brains. Encouraged by these results a few centres around the world have embarked in the design of clinical trials using recombinant Adeno-associated viruses for gene transfer.

For more information, please visit: http://www.eurekaselect.com/161003/article

EDITOR’S CHOICE – Inter-individual Variability in Activity of the Major Drug Metabolizing Enzymes in Liver Homogenates of 20 Individuals

Journal:  Current Drug Metabolism

Author(s): Shalenie P. den Braver-Sewradj, Michiel W. den Braver, Marc van Dijk, Yongjie Zhang, Stefan J. Dekker, Lukas Wijaya, Nico P.E. Vermeulen, Lysiane Richert, Jan N.M. Commandeur, J. Chris Vos*

Graphical Abstract:

 

Abstract:

Background: Inter-individual variability in hepatic drug metabolizing enzyme (DME) activity is a major contributor to heterogeneity in drug clearance and safety. Accurate data on expression levels and activities of DMEs is an important prerequisite for in vitro-in vivo extrapolation and in silico based predictions. Characterization and assessment of inter-correlations of the major DMEs cytochrome P450s (CYPs) and UDP-glucuronosyltransferases (UGTs) have been extensively documented, but simultaneous quantification including other major DMEs has been lacking.

Objective: Assessment of inter-donor variability and inter-correlations of CYPs, UGTs, sulfotransferases (SULTs), glutathione S-transferases (GSTs), NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH: quinone oxidoreductase 2 (NQO2) in a set of 20 individual liver homogenates.

Method: The main drug metabolizing isoforms of CYP and UGT have been reaction phenotype in individual liver microsomes and NQO1, NQO2, GSTT1 and GSTT2 in corresponding cytosol. In addition, we assessed overall SULT activity in liver cytosol using acetaminophen and 7-hydroxycoumarin as non-selective substrates and cytosolic GST activity using the non-selective substrate 1-chloro-2,4-dinitrobenzene (CDNB). Expression of GST isoforms was also assessed.

Results and Conclusion: While hepatic NQO1 activity was highly variable, NQO2 activity was more conserved. In addition, we found that of the hepatic GST isoforms, the variation in GSTM3 levels, which is poorly studied, was highest. The majority of significant correlations were found amongst CYP and UGT enzyme activities. The dataset presented provides the absolute quantification of the largest number of hepatic DME activities so far and constitute an essential resource for in silico toxicokinetic and metabolic modelling studies.

Read more here: http://www.eurekaselect.com/158885/article