scholarly journals Drug Design: Where We Are and Future Prospects

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 7061
Author(s):  
Giuseppe Zagotto ◽  
Marco Bortoli
Keyword(s):  
Drug Discovery ◽  
Metabolic Pathways ◽  
Future Prospects ◽  
Genetic Characteristics ◽  
Folding Intermediates ◽  
Biochemical Processes ◽  
Biological Meaning ◽  
The Central Nervous System ◽  
New Challenges ◽  
Important Progress

Medicinal chemistry is facing new challenges in approaching precision medicine. Several powerful new tools or improvements of already used tools are now available to medicinal chemists to help in the process of drug discovery, from a hit molecule to a clinically used drug. Among the new tools, the possibility of considering folding intermediates or the catalytic process of a protein as a target for discovering new hits has emerged. In addition, machine learning is a new valuable approach helping medicinal chemists to discover new hits. Other abilities, ranging from the better understanding of the time evolution of biochemical processes to the comprehension of the biological meaning of the data originated from genetic analyses, are on their way to progress further in the drug discovery field toward improved patient care. In this sense, the new approaches to the delivery of drugs targeted to the central nervous system, together with the advancements in understanding the metabolic pathways for a growing number of drugs and relating them to the genetic characteristics of patients, constitute important progress in the field.

Biological Role of Magnesium

1958 ◽  
Vol 4 (6) ◽  
pp. 429-451 ◽  
Author(s):  
A La Pleshchitser
Keyword(s):  
Atmospheric Oxygen ◽  
Biological Significance ◽  
Biological Role ◽  
Living Matter ◽  
Antagonistic Action ◽  
Biochemical Processes ◽  
The Central Nervous System ◽  
The Stability ◽  
Labile Equilibrium

Abstract Fersman (1934) commented on the relatively unimportant role of magnesium in biochemical processes. The comparatively limited radius of its ions, the stability and relative insolubility of its compounds prevent its taking an active part in the reactions of living matter. On the other hand, we have the statement of Vernadskii that in the plankton film of the ocean, in the ordinary accumulations and more massive growths, the amount of magnesium-containing chlorophyll must reach the order of 10-4 per cent by weight, if not higher, so that a small quantity of magnesium, entering into the composition of the chlorophyll-complex of the plankton, ultimately regulates the main part of the oxygenating function of living matter, the creation of free atmospheric oxygen. The material summarized by us likewise affords evidence of the importance of the role of magnesium in biological processes. All this, however, does not justify sharp differentiation between the biological role of magnesium and its role in biochemical processes. In all probability these processes are conditional to each other, although they are not identical processes. It is important to note the established and incontestable role of magnesium in many enzymatic processes in both the plant and animal kingdoms. The antagonistic action between magnesium and calcium, resulting from artificial changes in the ratios of these elements in soil, plants, and animals, can hardly occur under natural conditions, and, conversely, it must be assumed that a labile equilibrium between these elements is always maintained. The depressing action of magnesium ions on the central nervous system acquires considerable biological significance, since this permits the assumption that these ions in the animal organism may facilitate inhibitory processes in the nerve cell and insure the normal course of catabolic and anabolic processes. The narcotic and cholinolytic effects of magnesium constitute the basis for the wide therapeutic use of magnesium salts in medical practice.

Reproduction and Teratogenesis: Current Methods and Suggested Improvements

1975 ◽  
Vol 58 (4) ◽  
pp. 657-667
Author(s):  
James G Wilson
Keyword(s):  
Metabolic Pathways ◽  
Nonhuman Primates ◽  
Environmental Chemicals ◽  
Human Reproduction ◽  
Functional Evaluation ◽  
Endocrine Glands ◽  
Case Methods ◽  
Immunological Mechanisms ◽  
The Central Nervous System ◽  
Effect Level

Abstract The risks to human reproduction, particularly in regard to possible induction of birth defects, from present levels of environmental chemicals are thought to be low but in need of closer scrutiny than is now the case. Methods currently used to estimate the hazards to reproduction of new chemicals and drugs are reviewed and some shortcomings and potential sources of error are noted. Specific suggestions are made for improving existing methodology. In addition to the widely used treatment span encompassing all or most of the period of organogenesis, it is proposed that some exposure periods of shorter duration be added to avert possibly adaptative changes in maternal homeostatic systems. Greater diversity of test animals, beyond the rodent-rabbit species largely used today, is urged with the objective of better matching metabolic pathways in a test animal to those of man. The demonstration of an embryotoxicity effect-level must be regarded as essential in all tests, and once found this level should be used as the basis of extrapolating downward to find an acceptable tolerance level of dosage. More attention should be focused on postnatal functional evaluation after prenatal and perinatal exposure of test animals to environmental chemicals, especially those that might interfere with the maturation of the central nervous system, endocrine glands, and immunological mechanisms. The use of nonhuman primates should be reserved for the testing of drugs essential for use during human pregnancy or those likely to be taken inadvertently during early pregnancy, because of the scarcity of such animals and the high costs of doing meaningful tests with them.

scholarly journals Oligodendroglioma with Sarcomatous Transformation: Case Report and Literature Review

2019 ◽  
Vol 38 (02) ◽  
pp. 128-136
Author(s):  
Gonçalo Cerdeira Figueiredo ◽  
Célia Maria Pinheiro ◽  
Alfredo Luís Calheiros
Keyword(s):  
Spinal Metastasis ◽  
Poor Response ◽  
World Health ◽  
Rapid Progression ◽  
Who Grade ◽  
Genetic Characteristics ◽  
Oligodendroglial Component ◽  
The Central Nervous System ◽  
Grade Ii ◽  
Health Organization

AbstractOligodendrogliomas are infiltrative tumors of the central nervous system considered to be morphologically stable and to offer a better prognosis. Here, we describe the case of a 36-year-old man with an initial diagnosis of oligodendroglioma, World Health Organization (WHO) grade II, who presented transformation to a sarcomatous form, while maintaining the oligodendroglial component as well as the genetic characteristics of the initial tumor without having undergone any complementary treatments previously. Despite the favorable genetic characteristics, the tumor presented poor response to complementary treatments, and rapid progression, including spinal metastasis.

Secondary metabolites of the genus Crotalaria (Rattlepods) and their medicinal importance – A review

2020 ◽  
pp. 1-7
Author(s):  
Muhammad Sarwar Yaqub ◽  
Bushra Basher ◽  
Rozina Aslam
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acids ◽  
Wound Healing ◽  
Drug Discovery ◽  
Secondary Metabolites ◽  
Metabolic Pathways ◽  
Growth And Development ◽  
Chemical Compounds ◽  
Diverse Group ◽  
The World

This review describes the genus Crotalaria focusing on its secondary metabolites and their medicinal applications. The genus Crotalaria of Fabaceae or Leguminosae family have about 600 species which are distributed in tropic and sub-tropic regions of the world. They are medicinally important due to production of various compounds. Traditional early medicines and drug discovery were based on natural products. Organisms produce some chemical compounds by their metabolic pathways that are not necessary for their growth and development and are known as secondary metabolites. This diverse group of compounds is synthesized by algae, plants, animals and fungi. These metabolites consist of variety of compounds such as phenols, coumarins, terpenoids, flavonoids, alkaloids, steroids and fatty acids. Secondary metabolites obtained from crotalaria exhibit anticancer, anti-rheumatoid arthritis, anti-allergic, antioxidant, antimicrobial, antiaging and wound healing activities along with many other medicinal applications.

scholarly journals Upscaling of hiPS Cell–Derived Neurons for High-Throughput Screening

2016 ◽  
Vol 22 (3) ◽  
pp. 274-286
Author(s):  
Stefanie Traub ◽  
Heiko Stahl ◽  
Holger Rosenbrock ◽  
Eric Simon ◽  
Ralf Heilker
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Detection Sensitivity ◽  
Neuronal Markers ◽  
Downstream Target ◽  
Electrophysiological Recordings ◽  
Downstream Target Gene ◽  
The Central Nervous System ◽  
Induced Pluripotent

The advent of human-induced pluripotent stem (hiPS) cell–derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor–driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons. GRINCH cells displayed neuronal markers, and their functional activity could be demonstrated by electrophysiological recordings. In an application of GRINCH neurons, the brain-derived neurotrophic factor (BDNF)–mediated activation of tropomyosin receptor kinase (TrkB) was investigated as a promising drug target to treat synaptic dysfunctions. To assess the phosphorylation of endogenous TrkB in the GRINCH cells, the highly sensitive amplified luminescent proximity homogeneous assay LISA (AlphaLISA) format was established as a primary screen. A high-throughput reverse transcription (RT)–PCR format was employed as a secondary assay to analyze TrkB-mediated downstream target gene expression. In summary, an optimized differentiation protocol, highly efficient cell upscaling, and advanced assay miniaturization, combined with increased detection sensitivity, pave the way for a new generation of predictive cell-based drug discovery.

scholarly journals Registered Reports: Past, Present and Future

2020 ◽  
Author(s):  
Christopher D Chambers ◽  
Loukia Tzavella
Keyword(s):  
Journal Article ◽  
Research Process ◽  
Future Prospects ◽  
Multiple Stakeholders ◽  
Early Evidence ◽  
Wide Range ◽  
Universal Solution ◽  
Practical Guidance ◽  
New Challenges ◽  
First Time

Registered Reports are a form of empirical journal article in which study proposals are peer reviewed and pre-accepted before research is undertaken. By deciding which articles are published based on the question, theory, and proposed methods, Registered Reports offer a powerful remedy for a range of reporting and publication biases. Here we reflect on the history, progress and future prospects of the Registered Reports initiative, and also offer practical guidance for authors, reviewers, and editors encountering the format for the first time. While the key ingredients of pre-study review and results-blind acceptance are far from novel – and are already adopted independently in a variety of contexts – Registered Reports are the first mechanism to combine them into a mainstream policy that has won appeal with multiple stakeholders in the research process. We review early evidence that Registered Reports are working as intended, while at the same acknowledging that they are not a universal solution for irreproducibility. We also consider how the policies and practices surrounding Registered Reports are changing, or must change in future, to address limitations and adapt to new challenges. In spite of these caveats, we conclude that Registered Reports are promoting reproducibility, transparency and self-correction across a wide range of disciplines, and may help reshape how society evaluates research and researchers.

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