scholarly journals Predictability study of the pharmacodynamic properties of drugs in silico by the example of comparing data on the naphazoline clinical use and the results of computer modeling

2020 ◽  
Vol 22 (2) ◽  
pp. 171-176
Author(s):  
V. S. Ivanov ◽  
A. B. Seleznev ◽  
E. V. Ivchenko ◽  
D. V. Cherkashin ◽  
G. G. Kutelev ◽  
...  
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
In Silico ◽  
Gene Expression Regulation ◽  
Left Ventricular ◽  
The Body ◽  
Pharmacological Properties ◽  
Clinical Use ◽  
Web Resource ◽  
High Degree

The forecast of naphazoline pharmacological properties has been made using the PASS computer program and the ADVER-Pred web resource of the Way2Drug information and computing platform. Biological activity, mechanisms of action, toxic and side effects, as well as other types of activity of the studied drug associated with interaction with antitargets, metabolism and gene expression regulation have been determined. The results of the naphazoline pharmacological properties forecast obtained in silico have been compared with the information available in the literature about its systemic effects in clinical use and poisoning.It has been established that the studied chemical compound has a very wide spectrum of action, which is primarily associated with the stimulation of adrenoreceptors and imidazoline receptors located in many organs and tissues of the body. At the same time, other mechanisms of naphazoline action forecasted in silico allow us to determine possible directions for further research of its clinical use. Among the toxic and side effects, along with such known adverse events as effect on the central nervous system and arterial hypertension, in the clinical use of naphazoline special attention should be paid to the cardio-, hepato- and nephrotoxic effects forecasted with a high degree of probability. The prominent toxic effect of naphazoline can cause the occurrence of life- threatening conditions - acute cerebrovascular disorder, myocardial infarction, cardiac rhythm disorders, acute left ventricular failure. The obtained data confirm that the use of modern computer methods that provide an assessment of biological activity based on the drug-like compound graphic formula allows us to obtain a forecast with a high degree of confidence for both new pharmacological substances and for drugs approved for clinical use in order to clarify their pharmacological properties.

In silico platform for xenobiotics ADME-T pharmacological properties modeling and prediction. Part II: the body in a Hilbertian space

2009 ◽  
Vol 14 (7-8) ◽  
pp. 406-412 ◽  
Author(s):  
Alexandre Jacob ◽  
Jaturong Pratuangdejkul ◽  
Sébastien Buffet ◽  
Jean-Marie Launay ◽  
Philippe Manivet
Keyword(s):  
In Silico ◽  
The Body ◽  
Pharmacological Properties ◽  
Modeling And Prediction

scholarly journals In silico evaluation of some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors with pharmacokinetics ADMET and drug-likeness predictions

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Abdullahi Bello Umar ◽  
Adamu Uzairu ◽  
Gideon Adamu Shallangwa ◽  
Sani Uba
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Oral Bioavailability ◽  
In Silico ◽  
Braf Inhibitor ◽  
Docking Studies ◽  
Pharmacological Properties ◽  
Braf Inhibitors ◽  
Docking Analysis ◽  
Risk Parameters

Abstract Background The resistance of V600E-BRAF to the vemurafenib and the side effects of the identified inhibitors trigger the research for a novel and more potent anti-melanoma agents. In this study, virtual docking screening along with pharmacokinetics ADMET and drug-likeness predictions were combined to evaluate some 4-(quinolin-2-yl)pyrimidin-2-amine derivatives as potent V600E-BRAF inhibitors. Results Some of the selected compounds exhibited better binding scores and favorable interaction with the V600E-BRAF enzyme. Out of the screened compounds, two most potent (5 and 9) having good Rerank scores (− 128.011 and − 126.258) emerged as effective and potent V600E-BRAF inhibitors that outperformed the FDA-approved V600E-BRAF inhibitor (vemurafenib, − 118.607). Thus, the molecular docking studies revealed that the studied compounds showed competing for inhibition of V600E-BRAF with vemurafenib at the binding site and possessed better pharmacological parameters based on the drug-likeness rules filters for the oral bioavailability, and ADMET risk parameters. Conclusion The docking analysis, drug-likeness rules filters, and ADMET study identified compounds (5 and 9) as the best hits against V600E-BRAF kinase with enhanced pharmacological properties. This recommends that these compounds may be developed as potent anti-melanoma agents.

Evaluation of pipemidic acid derivatives for potential antimicrobial activity application: in silico studies on bioactivity

2020 ◽  
Vol 17 ◽  
Author(s):  
Mpho Phehello Ngoepe ◽  
Sharon Moeno
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
In Silico ◽  
Bacterial Infections ◽  
Protein Docking ◽  
Gamma Aminobutyric Acid ◽  
Pipemidic Acid ◽  
Quantum Chemical Descriptors ◽  
In Silico Studies ◽  
Tract Infections

Background: Pipemidic acid is a broad-spectrum quinolone antibacterial agent for the treatment of chronic urinary tract infections against both gram-positive and gram-negative bacteria. Both quinolone and fluoroquinolone antibiotics have been useful in combating bacterial infections. However, patients suffer severe side effects when they stop taking the medication. The piperazinyl region of pipemidic acid is highly responsible for the side effects. Objective: Therefore, the objective of this study is to design new compounds in which the piperazinyl region is masked by way of conjugation to benzoic acid derivatives Methods: In silico studies were conducted using AutoDockTools software for ligand-protein docking. The docking scores were compared to the parent pipemidic acid docked to Bacterial DNA (deoxyribonucleic acid) gyrase and GABA (gamma- Aminobutyric acid) receptor from the PDB (Protein Data Bank) database. Sites of metabolism, biological activity, quantum chemical descriptors and ADME (absorption, distribution, metabolism, and excretion) property predictions for each designed ligand were also evaluated Results: The docking studies and biological activity predictions showed good anti-infective properties (ligand PAR03) whilst also suggesting a reduction in GABA receptor agonist activity. The performance of PAR03 correlates with its electronic properties showing electrophilic character (can generate reactive Electrophilic Species (RES)). Conclusion: The results from this study indicate that modification of the piperazinyl region of pipemidic acid can be an effective way to improve the drug potency whilst also ensuring reduction of the associated side effects

scholarly journals Targeted Synthesis and Analysis of Biologically Active Azomethine Derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide

2021 ◽  
Vol 10 (2) ◽  
pp. 25-31
Author(s):  
A. S. Chiriapkin ◽  
I. P. Kodonidi ◽  
M. V. Larsky
Keyword(s):  
Biological Activity ◽  
Condensation Reaction ◽  
Spectral Characteristics ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Synthesis Conditions ◽  
Web Resource ◽  
Pharmacologically Active ◽  
Leading Compounds ◽  
Derivatives Of

Introduction. Azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide are acyclic precursors of biologically active compounds derived from 5,6,7,8-tetrahydro-3H-benzoteopheno[2,3-d]pyrimidine-4-one. Examples of these groups of compounds with different pharmacological properties are given in the literature, but their cytostatic effect is mainly described. These data and the preparative availability allow us to judge the prospects for further study and molecular design in a number of azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide. Optimization of methods for the synthesis and analysis of substances of this series and the identification of structure-activity relationship are of considerable interest for medical chemistry and pharmaceutical science. The resulting leading compounds will allow us to further develop laboratory requirements for the synthesis of an active pharmaceutical substance.Aim. To make a predict, optimize the synthesis conditions and develop a method for high performance liquid chromatography (HPLC) analysis of pharmacologically active azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide.Materials and methods. The prediction of biological activity was carried out through the web resource PASS Online. The synthesis of the target azomethines was carried out by the interaction of aromatic aldehydes with 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in an ethanol. The reaction was monitored by thin-layer chromatography (TLC). The determination of related impurities was done by HPLC. The analysis was carried out under the conditions of isocratic elution with a mobile phase of acetonitrile – water (70:30).Results and discussion. The results of the prediction of the biological activity of the constructed structures suggest the manifestation of cytostatic, antitubercular and anti-inflammatory activity characteristic of all target azomethines. The analysis of the reactivity revealed the influence of substituents of aldehydes contained in the aromatic core on the completeness of the condensation reaction. The spectral characteristics clearly confirmed the structure of the products, and the HPLC results showed the purity of the obtained substances, which is more than 95 %.Conclusion. As a result of the conducted studies, the structure of promising azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide was justified and the method of their synthesis and analysis by HPLC was optimized. In the future, the results of the research will allow us to identify the leading compounds with the specified pharmacological properties.

scholarly journals Biological Effects of Propolis on Cancer

2020 ◽  
Vol 8 (3) ◽  
pp. 573
Author(s):  
Hamide Doğan ◽  
Sibel Silici ◽  
Ahmet Ata Ozcimen
Keyword(s):  
Biological Activity ◽  
Side Effects ◽  
Biological Effects ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
In Vivo Studies ◽  
Pharmacological Properties ◽  
Bee Colony

Propolis is a special resin and wax material collected from the leaves and shells of trees, buds and shoots of plants by honey bees (Apis mellifera L.). In recent years, many researchers have studied the chemical composition, biological activity and pharmacological properties of propolis. The colour, odour and pharmacological properties of the propolis composition also vary as the composition changes depending on the plant, region, season and bee colony. Flavonoids, aromatic acids, phenolic acids and esters are the main compounds responsible for the biological activity of propolis. A number of studies have been conducted on the use of propolis or its active ingredients in the treatment of cancer. It has been observed that the use of propolis did not cause side effects according to in-vitro and in-vivo studies. Propolis should be extracted with different compounds for use in biological assays. The most commonly used compounds for extraction are ethanol, methanol, oil and water. A number of studies have been carried out showing the antitumor effect of propolis in cell culture and animal tests. The search for new drugs derived from natural products, which may function as chemotherapeutic agents and have low side effects, has increased in recent years. Combination with antioxidant therapy may improve the side effects of chemotherapy on leukocytes, liver and kidney, thus increasing the effect of chemotherapy with dose increase.

Vorklinische Untersuchung zur Organverteilung und Strahlenbelastung von Radiojod-Jodlisurid

1991 ◽  
Vol 30 (04) ◽  
pp. 137-140
Author(s):  
H. Flade ◽  
B. Johannsen ◽  
V. Pink ◽  
U. Herold ◽  
R. Harhammer ◽  
...  
Keyword(s):  
Radiation Dose ◽  
The Body ◽  
Organ Distribution ◽  
Clinical Use ◽  
Isolated Organs

The distribution in rats of 125l-iodolisuride was studied. Three rats each were sacrificed at fixed intervals between 5 min and 24 h p. i., and the radioactivity was measured in isolated organs and parts of the body. The organ distribution and biexponential blood disappearance were similar to values for unlabeled lisuride. The radiation dose was estimated for man assuming a 123l label. The resulting doses were comparable to those from other radiopharmaceuticals in clinical use.

Ruthenium Complexes for 1- and 2-Photon Photodynamic Therapy: From In Silico Prediction to In Vivo Applications

2020 ◽  
Author(s):  
Johannes Karges ◽  
Shi Kuang ◽  
Federica Maschietto ◽  
Olivier Blacque ◽  
Ilaria Ciofini ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
In Silico ◽  
Aqueous Solubility ◽  
The Body ◽  
Photon Absorption ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Photon Excitation ◽  
Polypyridine Complexes

<div>The use of photodynamic therapy (PDT) against cancer has received increasing attention overthe recent years. However, the application of the currently approved photosensitizers (PSs) is somehow limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E’)-4,4´-bisstyryl 2,2´-bipyridine ligands showed impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While non-toxic in the dark, these compounds were found phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and be able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2 Photon excitation.</div>

Biologically Active 2,5-Disubstituted-1,3,4-Oxadiazoles

2009 ◽  
Vol 2 (1) ◽  
pp. 390-406
Author(s):  
Harish Rajak ◽  
Murli Dhar Kharya ◽  
Pradeep Mishra
Keyword(s):  
Heterocyclic Compounds ◽  
Medical Literature ◽  
Biological Activities ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Clinical Use ◽  
Synthetic Drugs ◽  
Physiologic Activity ◽  
Pharmacologically Active

There are vast numbers of pharmacologically active heterocyclic compounds in regular clinical use. The presence of heterocyclic structures in diverse types of compounds is strongly indicative of the profound effects such structure exerts on physiologic activity, and recognition of this is abundantly reflected in efforts to find useful synthetic drugs. The 1,3,4-oxadiazole nucleus has emerged as one of the potential pharmacophore responsible for diverse pharmacological properties. Medical Literature is flooded with reports of a variety of biological activities of 2,5-Disubstituted-1,3,4-oxadiazoles. The present work is an attempt to summarize and enlist the various reports published on biologically active 2,5-disubstituted-1,3,4-oxadiazoles.

Biocompatible Polymers and their Potential Biomedical Applications: A Review

2019 ◽  
Vol 25 (34) ◽  
pp. 3608-3619 ◽  
Author(s):  
Uzma Arif ◽  
Sajjad Haider ◽  
Adnan Haider ◽  
Naeem Khan ◽  
Abdulaziz A. Alghyamah ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Biomedical Applications ◽  
Living System ◽  
Health Condition ◽  
The Body ◽  
Biocompatible Polymers ◽  
Nano Technology ◽  
Artificial Grafts ◽  
Immunological Reactions

Background: Biocompatible polymers are gaining great interest in the field of biomedical applications. The term biocompatibility refers to the suitability of a polymer to body and body fluids exposure. Biocompatible polymers are both synthetic (man-made) and natural and aid in the close vicinity of a living system or work in intimacy with living cells. These are used to gauge, treat, boost, or substitute any tissue, organ or function of the body. A biocompatible polymer improves body functions without altering its normal functioning and triggering allergies or other side effects. It encompasses advances in tissue culture, tissue scaffolds, implantation, artificial grafts, wound fabrication, controlled drug delivery, bone filler material, etc. Objectives: This review provides an insight into the remarkable contribution made by some well-known biopolymers such as polylactic-co-glycolic acid, poly(ε-caprolactone) (PCL), polyLactic Acid, poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), Chitosan and Cellulose in the therapeutic measure for many biomedical applications. Methods: : Various techniques and methods have made biopolymers more significant in the biomedical fields such as augmentation (replaced petroleum based polymers), film processing, injection modeling, blow molding techniques, controlled / implantable drug delivery devices, biological grafting, nano technology, tissue engineering etc. Results: The fore mentioned techniques and other advanced techniques have resulted in improved biocompatibility, nontoxicity, renewability, mild processing conditions, health condition, reduced immunological reactions and minimized side effects that would occur if synthetic polymers are used in a host cell. Conclusion: Biopolymers have brought effective and attainable targets in pharmaceutics and therapeutics. There are huge numbers of biopolymers reported in the literature that has been used effectively and extensively.

A Brief Review on the Development of Novel Potentially Active Azetidin-2-ones Against Cancer

2020 ◽  
Vol 24 (5) ◽  
pp. 473-486 ◽  
Author(s):  
Ligia S. da Silveira Pinto ◽  
Thatyana R. Alves Vasconcelos ◽  
Claudia Regina B. Gomes ◽  
Marcus Vinícius N. de Souza
Keyword(s):  
Side Effects ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
Present Review ◽  
Pharmacological Properties ◽  
Important Group ◽  
Wide Range ◽  
Anti Inflammatory

Azetidin-2-ones (&#946;-lactams) and its derivatives are an important group of heterocyclic compounds that exhibit a wide range of pharmacological properties such as antibacterial, anticancer, anti-diabetic, anti-inflammatory and anticonvulsant. Efforts have been made over the years to develop novel congeners with superior biological activities and minimal potential for undesirable side effects. The present review aimed to highlight some recent discoveries (2013-2019) on the development of novel azetidin-2-one-based compounds as potential anticancer agents.

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