scholarly journals Overview of Biologically Active Nucleoside Phosphonates

2021 ◽  
Vol 8 ◽  
Author(s):  
Elisabetta Groaz ◽  
Steven De Jonghe
Keyword(s):  
Drug Design ◽  
Infectious Diseases ◽  
Metabolic Activation ◽  
P2y Receptors ◽  
Biologically Active ◽  
Future Design ◽  
Bioisosteric Replacement ◽  
P2x And P2y Receptors ◽  
Structural Concept ◽  
Labile P

The use of the phosphonate motif featuring a carbon-phosphorous bond as bioisosteric replacement of the labile P–O bond is widely recognized as an attractive structural concept in different areas of medicinal chemistry, since it addresses the very fundamental principles of enzymatic stability and minimized metabolic activation. This review discusses the most influential successes in drug design with special emphasis on nucleoside phosphonates and their prodrugs as antiviral and cancer treatment agents. A description of structurally related analogs able to interfere with the transmission of other infectious diseases caused by pathogens like bacteria and parasites will then follow. Finally, molecules acting as agonists/antagonists of P2X and P2Y receptors along with nucleotidase inhibitors will also be covered. This review aims to guide readers through the fundamentals of nucleoside phosphonate therapeutics in order to inspire the future design of molecules to target infections that are refractory to currently available therapeutic options.

Fusion Protein Targeted Antiviral Peptides: Fragment-Based Drug Design (FBDD) Guided Rational Design of Dipeptides Against SARS-CoV-2

2020 ◽  
Vol 21 (10) ◽  
pp. 938-947
Author(s):  
Sounik Manna ◽  
Trinath Chowdhury ◽  
Piyush Baindara ◽  
Santi M. Mandal
Keyword(s):  
Public Health ◽  
Drug Design ◽  
Infectious Diseases ◽  
Fusion Protein ◽  
Fusion Process ◽  
Viral Fusion ◽  
Enveloped Viruses ◽  
Antiviral Peptides ◽  
Target Sites ◽  
Tract Infections

: Infectious diseases caused by viruses have become a serious public health issue in the recent past, including the current pandemic situation of COVID-19. Enveloped viruses are most commonly known to cause emerging and recurring infectious diseases. Viral and cell membrane fusion is the major key event in the case of enveloped viruses that is required for their entry into the cell. Viral fusion proteins play an important role in the fusion process and in infection establishment. Because of this, the fusion process targeting antivirals become an interest to fight against viral diseases caused by the enveloped virus. Lower respiratory tract infections casing viruses like influenza, respiratory syncytial virus (RSV), and severe acute respiratory syndrome coronavirus (SARS-CoV) are examples of such enveloped viruses that are at the top in public health issues. Here, we summarized the viral fusion protein targeted antiviral peptides along with their mechanism and specific design to combat the viral fusion process. The pandemic COVID-19, severe respiratory syndrome disease is an outbreak worldwide. There are no definitive drugs yet, but few are in on-going trials. Here, an approach of fragmentbased drug design (FBDD) methodology is used to identify the broad spectrum agent target to the conserved region of fusion protein of SARS CoV-2. Three dipeptides (DL, LQ and ID) were chosen from the library and designed by the systematic combination along with their possible modifications of amino acids to the target sites. Designed peptides were docked with targeted fusion protein after energy minimization. Results show strong and significant binding affinity (DL = -60.1 kcal/mol; LQ = - 62.8 kcal/mol; ID= -71.5 kcal/mol) during interaction. Anyone of the active peptides from the developed libraries may help to block the target sites competitively to successfully control COVID-19.

Isoselenocyanates: Synthesis and Their Use for Preparing Selenium-Based Heterocycles

Synthesis ◽  
2021 ◽  
Author(s):  
Stefan H. Bossmann ◽  
Raul Neri
Keyword(s):  
Biological Activity ◽  
Infectious Diseases ◽  
Cancer Cells ◽  
Multicomponent Reactions ◽  
Oxidative Cyclization ◽  
Biologically Active ◽  
Organoselenium Compounds ◽  
X Ray ◽  
Synthetic Work

AbstractIsoselenocyanates (ISCs) are a class of organoselenium compounds that have been recognized as potential chemotherapeutic and chemopreventative agents against cancer(s) and infectious diseases. ISC compounds are chemically analogous to their isosteric relatives, isothiocyanates (ITCs); however, they possess increased biological activity, such as enhanced cytotoxicity against cancer cells. ISCs not only serve as significant products, but also as precursors and essential intermediates for a variety of organoselenium compounds, such as selenium-containing heterocycles, which are biologically active. While syntheses of ISCs have become less difficult to accomplish, the syntheses of selenium-containing heterocycles are often difficult due to the use of highly toxic selenium reagents. Because of this, ISCs can serve as versatile reagents for the preparation of these heterocycles. In this review, the classical and recent syntheses of ISCs will be discussed, along with notable and recent synthetic work employing ISCs to access novel selenium-containing heterocycles.1 Introduction1.1 Selenium and Health2 Isoselenocyanates2.1 Preparation of Isoselenocyanates3 Selenium-Containing Heterocycles3.1 Notable Synthetic Work3.2 Recent Synthetic Work3.2.1 Synthesis of N-(3-Methyl-4-phenyl-3H-selenazol-2-ylidene)benzamide­ Derivatives3.2.2 Synthesis and X-ray Studies of Diverse Selenourea Derivatives3.2.3 Synthesis of Heteroarene-Fused [1,2,4]Thiadiazoles/Selenadiazoles via Iodine-Promoted [3+2] Oxidative Cyclization3.2.4 2-Amino-1,3-selenazole Derivatives via Base-Promoted Multicomponent Reactions4 Conclusion

scholarly journals John Daly Lecture: Structure-guided Drug Design for Adenosine and P2Y Receptors

2015 ◽  
Vol 13 ◽  
pp. 286-298 ◽  
Author(s):  
Kenneth A. Jacobson ◽  
Zhan-Guo Gao ◽  
Silvia Paoletta ◽  
Evgeny Kiselev ◽  
Saibal Chakraborty ◽  
...  
Keyword(s):  
Drug Design ◽  
P2y Receptors

scholarly journals PLANT-BASED MILK ANALOGUES IN THE NUTRITION OF PEOPLE WITH NUTRITION-DEPENDENT NON-INFECTIOUS DISEASES

2020 ◽  
Vol 14 (2) ◽  
Author(s):  
N. Pritulska ◽  
I. Motuzka ◽  
A. Koshelnyk ◽  
M. Jarossová ◽  
A. Lacková
Keyword(s):  
Infectious Diseases ◽  
Raw Materials ◽  
Food Products ◽  
Domestic Market ◽  
Biologically Active ◽  
Raw Material ◽  
Fenugreek Seeds ◽  
Product Group ◽  
Wide Range ◽  
Treatment Procedures

A recent tendency in Ukraine is the changes in the structure of food consumption, which are caused by the reduced consumption of some product groups and by their decreasing quality. A persisting problem is that affordable and easy-to-consume food products made with due consideration of the needs of patients with certain categories of diseases can hardly be found on the domestic market. The products present on the domestic market are all imported, available in a limited assortment, very expensive, and not customised to suit all the specific needs of human metabolism. Approaches to the nutrition of patients with certain types of nutrition-dependent and non-infectious diseases have been analysed. It has been established that аn effective component in the diet of patients with non-infectious diseases can be plant-based milk analogues. It has been determined how important it is to use domestic raw materials: it will contribute to expanding domestic production, will help the gross domestic product growth, and will reduce the product’s costs, thus reducing the costs of diagnostic and treatment procedures. It has been established that the assortment of plant-based milk analogues is constantly expanding. The vegetable raw material conventionally used to make this product group has been analysed. It has been shown that fenugreek seeds can be most effectively used to make special food products (in particular, plant-based milk analogues) for the nutritional support of patients with non-infectious diseases. This is feasible due to the availability of the raw material, simple cultivating conditions, the chemical composition of the product (e. g. a wide range of biologically active substances), low costs of the product when it is made from domestic raw materials, and the simple production technology. It is expected that manufacture of milk analogues from fenugreek seeds will widen the assortment of this product group, and satisfy the target consumers’ needs of safe and high quality products that offer an alternative to imports.

Natural DNA Intercalators as Promising Therapeutics for Cancer and Infectious Diseases

2020 ◽  
Vol 20 (1) ◽  
pp. 19-32 ◽  
Author(s):  
Martyna Godzieba ◽  
Slawomir Ciesielski
Keyword(s):  
Infectious Diseases ◽  
Therapeutic Potential ◽  
Modern Medicine ◽  
Biologically Active ◽  
Substantial Part ◽  
Unhealthy Lifestyle ◽  
Natural Origin ◽  
Chemical Structures ◽  
Small Molecule Ligands ◽  
Improper Use

Cancer and infectious diseases are one of the greatest challenges of modern medicine. An unhealthy lifestyle, the improper use of drugs, or their abuse are conducive to the increase of morbidity and mortality caused by these diseases. The imperfections of drugs currently used in therapy for these diseases and the increasing problem of drug resistance have forced a search for new substances with therapeutic potential. Throughout history, plants, animals, fungi and microorganisms have been rich sources of biologically active compounds. Even today, despite the development of chemistry and the introduction of many synthetic chemotherapeutics, a substantial part of the new compounds being tested for treatment are still of natural origin. Natural compounds exhibit a great diversity of chemical structures, and thus possess diverse mechanisms of action and molecular targets. Nucleic acids seem to be a good molecular target for substances with anticancer potential in particular, but they may also be a target for antimicrobial compounds. There are many types of interactions of small-molecule ligands with DNA. This publication focuses on the intercalation process. Intercalators are compounds that usually have planar aromatic moieties and can insert themselves between adjacent base pairs in the DNA helix. These types of interactions change the structure of DNA, leading to various types of disorders in the functioning of cells and the cell cycle. This article presents the most promising intercalators of natural origin, which have aroused interest in recent years due to their therapeutic potential.

scholarly journals Telodendrimer-Based Macromolecular Drug Design using 1,3-Dipolar Cycloaddition for Applications in Biology

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 857 ◽  
Author(s):  
Hossein Yazdani ◽  
Esha Kaul ◽  
Ayoob Bazgir ◽  
Dusica Maysinger ◽  
Ashok Kakkar
Keyword(s):  
Polyethylene Glycol ◽  
Drug Design ◽  
Cell Survival ◽  
Active Agent ◽  
Water Soluble ◽  
Biologically Active ◽  
Nitrile Oxide ◽  
Dipolar Cycloaddition ◽  
U251 Cell ◽  
Macromolecular Drug

An architectural polymer containing hydrophobic isoxazole-based dendron and hydrophilic polyethylene glycol linear tail is prepared by a combination of the robust ZnCl2 catalyzed alkyne-nitrile oxide 1,3-dipolar cycloaddition and esterification chemistry. This water soluble amphiphilic telodendrimer acts as a macromolecular biologically active agent and shows concentration dependent reduction of glioblastoma (U251) cell survival.

ISO-CC-005: A phase I/II study of Modufolin (MTHF) in combination with 5-FU, irinotecan, and oxaliplatin ± bevacizumab in patients with metastasizing colorectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 838-838
Author(s):  
Helena Anna Taflin ◽  
Karin M E Ganlov ◽  
Tormod Kyrre Guren ◽  
Christos Papadimitrou ◽  
Nikolaos K. Kentepozidis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Active Form ◽  
Metabolic Activation ◽  
Individual Variability ◽  
Biologically Active ◽  
Chemotherapy Treatment ◽  
Time To Death ◽  
Dose Levels ◽  
Clinical Trial Information

838 Background: Chemotherapy treatment of Colorectal Cancer, often include 5-Fluorouracil (5- FU). 5-FU inhibits the enzyme thymidylate synthase (TS), stopping the supply of thymidine for DNA synthesis. 5-FU is always combined with a folate, which enhances the 5-FU effect. Marketed folates such as LV/L-LV are prodrugs needing enzymatic conversion. Modufolin is the natural, biologically active form of the folates and is expected to be efficacious in a larger proportion of patients with less inter- and intra-individual variability Methods: ISO-CC-005 is a multi-center, phase I/II study in mCRC patients eligible for 5-FU/folate therapy alone or in combination with irinotecan or oxaliplatin ± bevacizumab. The study investigates safety and tolerability of Modufolin at 4 dose levels by analysing the number and severity of AEs, SAEs and DLTs. Efficacy is evaluated as ORR after four cycles of chemotherapy. Gene expression, deoxyuridine levels as an indirect marker of TS inhibition and time to death is also investigated. Three to six patients per cohort are included. All receives Modufolin twice every two weeks during at least four cycles of chemotherapy. Results: Today, 42 patients have been enrolled and 40 have initiated treatment. 13 are 1st line patients, 16 are in 2nd line, 10 are in 3rd line and 1 is in 5th treatment line. 19 SAEs have been reported in 12 patients, 3 of these were judged as at least possibly related to Modufolin. No SAE were judged as solely related to Modufolin. 31 patients have today been evaluated for efficacy. ORR 1st line patients (n=12) All 50% (6 PR, 6 SD) Patients with Modufolin dose ≥60 mg/m2 71% (5 PR, 2 SD) Patients with Modufolin dose ≥60 mg/m2 + oxaliplatin 100% (3 PR) Conclusions: The lack of need for metabolic activation makes Modufolin a better candidate than LV/L-LV for improved outcome of 5-FU-based chemotherapy regimens in mCRC. The ISO-CC-005 study evaluates Modufolin in combination with 5-FU, irinotecan, oxaliplatin ± bevacizumab in mCRC patients in 4 countries in Europe. The results, so far, for both safety and efficacy seems promising. Clinical trial information: NCT02244632.

scholarly journals Blood exosomes as new biomarkers of infectious diseases

2021 ◽  
Vol 5 (11) ◽  
pp. 744-748
Author(s):  
A.V. Ageykin ◽  
◽  
A.V. Gorelov ◽  
D.V. Usenko ◽  
V.L. Melnikov ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Extracellular Vesicles ◽  
Biological Membrane ◽  
General Information ◽  
Biologically Active ◽  
Main Function ◽  
Adaptive Immune ◽  
Microscopic Features ◽  
New Biomarkers ◽  
Russian Medical

Extracellular vesicles are biological membrane objects having a size of less than 1000 nm, the main function of which is the transport of various biologically active molecules. They can also provide intercellular interactions and perform other biological functions. The review provides general information about extracellular vesicles, their varieties, morphological and microscopic features. The article gives various classifications of extracellular vesicles and considers pathogenetic features of the exosome interaction with viruses. Adding that the specific patterns of the introduction, interaction and identification of exosomes affected by viruses are determined on the example of a number of viruses. The possibility of extracellular vesicles to penetrate the blood-brain barrier, coordinating the immune system activity in response to the viral effects, is indicated. Exosome ability to mediate intercellular communication through innate and adaptive immune responses is discussed. The paper considers the prospects of using exosomes in the preventive diagnosis of infectious diseases, which will allow using exomes as the main diagnostic tool and determining the stage of infectious disease progression. The review provides information about the study of the exosome therapeutic possibilities. The authors have drawn conclusions about the importance of continuing the study of exosomes for use in the diagnosis and treatment of infectious diseases. KEYWORDS: viruses, extracellular vesicles, apoptotic bodies of exosomes, ectosomes, diagnosis, treatment. FOR CITATION: Ageykin A.V., Gorelov A.V., Usenko D.V., Melnikov V.L. Blood exosomes as new biomarkers of infectious diseases. Russian Medical Inquiry. 2021;5(11):744–748 (in Russ.). DOI: 10.32364/2587-6821-2021-5-11-744-748.

scholarly journals Design aspects of the combined medicinal product with multifunctional action based on herbal drugs

2021 ◽  
pp. 57-67
Author(s):  
С. А. Котов ◽  
Т. М. Гонтова ◽  
А. Г. Котов
Keyword(s):  
Amino Acids ◽  
Drug Design ◽  
Medicinal Product ◽  
Correlation Coefficient ◽  
Rank Correlation ◽  
Allergic Diseases ◽  
Biologically Active ◽  
Herbal Drugs ◽  
Spearman’S Rank Correlation ◽  
Spearman’S Rank Correlation Coefficient

Combined herbal medicines for the treatment and prevention of allergic diseases are perspective substitutes for the «classic» drugs of H-1 receptor blockers of the 1st and 2nd generation. Literary-logical methods are quite effectively used for scientifically justified design of these drugs, namely phytopharmacological drug design (PPD) and phytochemical drug design (PCD). The aim of the work – the search for ways of the scientifically justified design of a combined multifunctional medicine based on the bur-marigold, which normalizes the functioning of the body's defence systems, increases the body's nonspecific resistance, normalizes the immune status using literary-logical and statistical methods of analysis. The design of the preparation was carried out using literature data for PPD and experimental and literature data for PCD. Statistical processing method – Spearman's rank correlation coefficient was used. Design aspects of the combined herbal medicine, which includes a bur-marigold herb, calendula flowers, hawthorn leaves and flowers were considered using of a system-comparative analysis of information and its processing by the method of the Spearman's rank correlation coefficient determination. When PCD development of various combinations of herbal drugs, information about the content of such biologically active substances (BAS) as flavonoids, oxycinnamic acids, polyphenols, triterpenes, proteins/amino acids, polysaccharides was used. When PPD development the spectra of pharmacological activity were determined and a quantitative assessment to them in the system of marks for each of the herbal drug of the combined medicine was given. The PCD and PPD data into the matrix for calculating the Spearman rank correlation coefficient of the «action–sum of BAS» was entered. As a result, a strong, direct and statistically significant correlation relation (p from 0.924 to 0.997) between the content of oxycinnamic acids, polyphenols, triterpenes, proteins/amino acids, polysaccharides and such pharmacological actions as capillary-strengthening, anti-inflammatory, immunostimulating; choleretic, hepatoprotective, improving metabolism; diuretic, hypotensive, sedative, tonic, desensitizing, antipruritic, reparative for the studied herbal combinations was found. The obtained results of the PCD and PPD development as well as the study of the correlation «action–sum of BAS» by calculating the Spearman's rank correlation coefficient, this suggests the developed combined herbal medicinal product with multifunctional action is perspective in the complex therapy of allergic diseases accompanied by a decrease in the body's resistance and immunostatus.

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