scholarly journals l-Arginine Improves Solubility and ANTI SARS-CoV-2 Mpro Activity of Rutin but Not the Antiviral Activity in Cells

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6062
Author(s):  
Luca Sancineto ◽  
Carmine Ostacolo ◽  
David Ortega-Alarcon ◽  
Ana Jimenez-Alesanco ◽  
Laura Ceballos-Laita ◽  
...  
Keyword(s):  
Water Solubility ◽  
Pharmaceutical Preparations ◽  
Experimental Investigations ◽  
Active Principle ◽  
Pharmacological Activities ◽  
Solubility In Water ◽  
Solubility Improvement ◽  
Starting Point ◽  
Pharmacokinetic Properties ◽  
Good Starting Point

The COVID-19 pandemic outbreak prompts an urgent need for efficient therapeutics, and repurposing of known drugs has been extensively used in an attempt to get to anti-SARS-CoV-2 agents in the shortest possible time. The glycoside rutin shows manifold pharmacological activities and, despite its use being limited by its poor solubility in water, it is the active principle of many pharmaceutical preparations. We herein report our in silico and experimental investigations of rutin as a SARS-CoV-2 Mpro inhibitor and of its water solubility improvement obtained by mixing it with L-arginine. Tests of the rutin/L-arginine mixture in a cellular model of SARS-CoV-2 infection highlighted that the mixture still suffers from unfavorable pharmacokinetic properties, but nonetheless, the results of this study suggest that rutin might be a good starting point for hit optimization.

scholarly journals Oxyresveratrol: Sources, Productions, Biological Activities, Pharmacokinetics, and Delivery Systems

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4212
Author(s):  
Kittisak Likhitwitayawuid
Keyword(s):  
Water Solubility ◽  
Biological Activities ◽  
Delivery Systems ◽  
Protective Effects ◽  
Pharmacological Activities ◽  
Plant Materials ◽  
Research Attention ◽  
Pharmacokinetic Properties ◽  
Simple Chemical ◽  
Oral Availability

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.

scholarly journals Biofilms Production from Avocado Waste

2021 ◽  
Vol 25 ◽  
Author(s):  
Horacio Sánchez ◽  
Wilmer Ponce ◽  
Beatriz Brito ◽  
William Viera ◽  
Ricardo Baquerizo ◽  
...  
Keyword(s):  
Modulus Of Elasticity ◽  
Water Solubility ◽  
Film Formation ◽  
Persea Americana ◽  
Gelatinization Temperature ◽  
Water Density ◽  
Casting Method ◽  
Solubility In Water ◽  
Starting Point ◽  
Starch Yield

Objective: To obtain biofilms from starch and cellulose present in the avocado (Persea americana) peel and seed. Materials and methods: The starch characterization included humidity, gelatinization temperature, paste clarity, absorption index, solubility index, swelling power, amylose, amylopectin, amount, and starch yield. Five mixtures were made with 3 g of starch, 5 mL of 30 % NaOH (w/v), 3 g of cellulose, and different proportions for glycerin: 2 g; 2.5 g; 3 g; 3.5 g; 4 g, and PVA: 2 g, 3 g, 4 g, 5 g, and 6 g. Films were formed on acrylic plates, using the casting method. The bioplastic was characterized in terms of moisture, solubility in water, density, thickness, biodegradability, stress, deformation, and modulus of elasticity. Results and discusión: The addition of cellulose to the mixture does not contribute to film formation, unlike PVA which did. The film had the best physical appearance with a mixture of 2 g of glycerin and 6 g of PVA. The bioplastic characterization was 23.43 % humidity, 39.39 % for water solubility, 1.52 g/cm3 density, 0.58 mm thickness, 21.03 % weight loss for the biodegradability test, 1.53 MPa for tension, 21.25 % deformation, and 10,04 MPa for the modulus of elasticity. Conclusions: The bioplastic obtained did not show the resistance of traditional plastic. However, the results obtained serve as a starting point for the realization of other formulations, aimed at producing a bioplastic capable of competing with its synthetic relatives.

scholarly journals Synthesis and Antiviral Activity of Novel 1,3,4-Thiadiazole Inhibitors of DDX3X

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3988 ◽  
Author(s):  
Brai ◽  
Ronzini ◽  
Riva ◽  
Botta ◽  
Zamperini ◽  
...  
Keyword(s):  
Aqueous Solubility ◽  
Biological Profile ◽  
New Family ◽  
Dead Box ◽  
Starting Point ◽  
Pharmacokinetic Properties ◽  
Good Starting Point ◽  
Further Development ◽  
Micromolar Range

The human ATPase/RNA helicase X-linked DEAD-box polypeptide 3 (DDX3X) emerged as a novel therapeutic target in the fight against both infectious diseases and cancer. Herein, a new family of DDX3X inhibitors was designed, synthesized, and tested for its inhibitory action on the ATPase activity of the enzyme. The potential use of the most promising derivatives it has been investigated by evaluating their anti-HIV-1 effects, revealing inhibitory activities in the low micromolar range. A preliminary ADME analysis demonstrated high metabolic stability and good aqueous solubility. The promising biological profile, together with the suitable in vitro pharmacokinetic properties, make these novel compounds a very good starting point for further development.

scholarly journals Discovery and Optimization of Selective Inhibitors of Meprin α (Part I)

2021 ◽  
Vol 14 (3) ◽  
pp. 203 ◽  
Author(s):  
Shurong Hou ◽  
Juan Diez ◽  
Chao Wang ◽  
Christoph Becker-Pauly ◽  
Gregg B. Fields ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
De Novo ◽  
Selective Inhibitors ◽  
Preclinical Development ◽  
Starting Point ◽  
Good Starting Point ◽  
Parallel Screening ◽  
Low Cytotoxicity

Meprin α and β are zinc-dependent proteinases implicated in multiple diseases including cancers, fibrosis, and Alzheimer’s. However, until recently, only a few inhibitors of either meprin were reported and no inhibitors are in preclinical development. Moreover, inhibitors of other metzincins developed in previous years are not effective in inhibiting meprins suggesting the need for de novo discovery effort. To address the paucity of tractable meprin inhibitors we developed ultrahigh-throughput assays and conducted parallel screening of >650,000 compounds against each meprin. As a result of this effort, we identified five selective meprin α hits belonging to three different chemotypes (triazole-hydroxyacetamides, sulfonamide-hydroxypropanamides, and phenoxy-hydroxyacetamides). These hits demonstrated a nanomolar to micromolar inhibitory activity against meprin α with low cytotoxicity and >30-fold selectivity against meprin β and other related metzincincs. These selective inhibitors of meprin α provide a good starting point for further optimization.

scholarly journals Advances on the Implementation of Circular Economy Techniques in Rural Areas in Colombia under a Sustainable Development Framework

2021 ◽  
Vol 13 (7) ◽  
pp. 3816
Author(s):  
Javier Rodrigo-Ilarri ◽  
Camilo-A. Vargas-Terranova ◽  
María-Elena Rodrigo-Clavero ◽  
Paula-A. Bustos-Castro
Keyword(s):  
Sustainable Development ◽  
Waste Management ◽  
Circular Economy ◽  
Rural Areas ◽  
Development Framework ◽  
Starting Point ◽  
Management Plans ◽  
Good Starting Point ◽  
Depressed Regions ◽  
First Time

For the first time in the scientific literature, this research shows an analysis of the implementation of circular economy techniques under sustainable development framework in six municipalities with a depressed economy in Colombia. The analysis is based on solid waste data production at a local scale, the valuation of the waste for subsequent recycling, and the identification and quantification of the variables associated with the treatment and final disposal of waste, in accordance with the Colombian regulatory framework. Waste generation data are obtained considering three different scenarios, in which a comparison between the simulated values and those established in the management plans are compared. Important differences have been identified between the waste management programs of each municipality, specifically regarding the components of waste collection, transportation and disposal, participation of environmental reclaimers, and potential use of materials. These differences are fundamentally associated with the different administrative processes considered for each individual municipality. This research is a good starting point for the development of waste management models based on circular economy techniques, through the subsequent implementation of an office tool in depressed regions such as those studied.

Industry-Sponsored Medical Education — In the Quest for Professional Integrity and Legal Certainty

2007 ◽  
Vol 14 (4) ◽  
pp. 313-319
Author(s):  
Benedikt Buchner
Keyword(s):  
Medical Education ◽  
Self Regulation ◽  
State Regulation ◽  
General Question ◽  
Legal Certainty ◽  
European Directive ◽  
Starting Point ◽  
Good Starting Point ◽  
Advertising Law ◽  
The Right

AbstractIndustry-sponsored medical education is a much disputed issue. So far, there has been no regulatory framework which provides clear and definite rules as to whether and under what circumstances the sponsorship of medical education is acceptable. State regulation does not exist, or confines itself to a very general principle. Professional regulation, even though applied frequently, is rather vague and indefinite, raising the general question as to whether self-regulation is the right approach at all. Certainly, self-regulation by industry cannot and should not replace other regulatory approaches. Ultimately, advertising law in general and the European Directive 2001/83/EC specifically, might be a good starting point in providing legal certainty and ensuring the independence of medical education. Swiss advertising law illustrates how the principles of the European Directive could be implemented clearly and unambiguously.

scholarly journals Multiple Myeloma Inhibitory Activity of Plant Natural Products

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2678
Author(s):  
Karin Jöhrer ◽  
Serhat Sezai Ҫiҫek
Keyword(s):  
Multiple Myeloma ◽  
Natural Products ◽  
Myeloma Cell ◽  
Myeloma Cell Line ◽  
Antiproliferative Effects ◽  
Plant Natural Products ◽  
Starting Point ◽  
Human Myeloma Cell Line ◽  
Group A ◽  
Good Starting Point

A literature search on plant natural products with antimyeloma activity until the end of 2020 resulted in 92 compounds with effects on at least one human myeloma cell line. Compounds were divided in different compound classes and both their structure–activity-relationships as well as eventual correlations with the pathways described for Multiple Myeloma were discussed. Each of the major compound classes in this review (alkaloids, phenolics, terpenes) revealed interesting candidates, such as dioncophyllines, a group of naphtylisoquinoline alkaloids, which showed pronounced and selective induction of apoptosis when substituted in position 7 of the isoquinoline moiety. Interestingly, out of the phenolic compound class, two of the most noteworthy constituents belong to the relatively small subclass of xanthones, rendering this group a good starting point for possible further drug development. The class of terpenoids also provides noteworthy constituents, such as the highly oxygenated diterpenoid oridonin, which exhibited antiproliferative effects equal to those of bortezomib on RPMI8226 cells. Moreover, triterpenoids containing a lactone ring and/or quinone-like substructures, e.g., bruceantin, whitaferin A, withanolide F, celastrol, and pristimerin, displayed remarkable activity, with the latter two compounds acting as inhibitors of both NF-κB and proteasome chymotrypsin-like activity.

COVID-19, Business, and Human Rights

2021 ◽  
Vol 23 (5) ◽  
pp. 433-449
Author(s):  
Surya Deva
Keyword(s):  
Human Rights ◽  
Full Range ◽  
International Human Rights Law ◽  
Human Rights Law ◽  
International Human Rights ◽  
Economic Problems ◽  
Business And Human Rights ◽  
Starting Point ◽  
Good Starting Point ◽  
International Human

Abstract COVID-19 has affected the full range of human rights, though some rights holders have experienced a disproportionate impact. This has triggered debate about the respective obligations and responsibilities of states and business enterprises under international human rights law. Against this backdrop, this article examines critically whether the “protect, respect and remedy” framework operationalised by the UN Guiding Principles on Business and Human Rights is “fit for the purpose” to deal with the COVID-19 crisis. I argue that while the UNGPs’ framework provides a good starting point, it is inadequate to bring transformative changes to overcome deep-rooted socio-economic problems exposed by this pandemic. Realising human rights fully would not only require harnessing the potential of states’ tripartite obligations, but also move beyond limiting the responsibility of businesses to respect human rights.

Water Depollution Control : A Gateway to Reaction Monitoring and Analytical Chemistry

2021 ◽  
Author(s):  
Martin Tiano ◽  
Max Roose
Keyword(s):  
Analytical Chemistry ◽  
Undergraduate Students ◽  
Environmental Chemistry ◽  
Organic Pollutant ◽  
Internal Standard ◽  
Experimental Session ◽  
Reaction Monitoring ◽  
Starting Point ◽  
Good Starting Point ◽  
Magnetite Particles

<div>We present here an experimental session for undergraduate students, based on the reaction monitoring of the degradation of an organic pollutant (para-nitrophenol) by a Fenton-like reaction, catalysed by magnetite particles. <br></div><div>During the session, students realized a follow-up of the reaction by Gas Chromatography with an internal standard, and by UV-Visible spectrophotometry. <br></div>This session was a good starting point to numerous discussions about analytical chemistry, environmental chemistry.

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