The aim of this study is to improve the aqueous solubility of a group of compounds without interfering with their bioassay as well as to create a relevant prediction model. A series of 55 potential small-molecule inhibitors of tumor necrosis factor-alpha (TNF-α; SPD304 and 54 analogues), many of which cannot be bioassayed because of their poor solubility, was used for this purpose. The solubility of many of the compounds was sufficiently improved to allow measurement of their respective dissociation constants (K). Parameters such as dissolution time, initial state of the solute (solid/liquid), co-solvent addition (DMSO and PEG3350), and sample filtration were evaluated. Except for filtration, the remaining parameters affected aqueous solubility, and a solubilization protocol was established according to these. The aqueous solubility of the 55 compounds in 5% DMSO was measured with this protocol, and a predictive quantitative structure property relationship model was developed and fully validated based on these data. This classification model separates the insoluble from the soluble compounds and predicts the solubility of potential small-molecule inhibitors of TNF-α in aqueous solution (containing 5% DMSO as co-solvent) with an accuracy of 81.2%. The domain of applicability of the model indicates the type of compounds for which estimation of aqueous solubility can be confidently predicted.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1177/2472555217712507 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Modeling of CO solubility and partial pressure in blended diisopropanolamine and 2-amino-2-methylpropanol solutions via response surface methodology and artificial neural network.
Sci Rep
January 2025
School of Chemical, Petroleum and Gas Engineering, Iran University of Science and Technology, P.O. Box: 16765-163, Tehran, Iran.
In this study, Response Surface Methodology (RSM) and Artificial Neural Networks (ANN) were developed to estimate the equilibrium solubility and partial pressure of CO in blended aqueous solutions of diisopropanolamine (DIPA) and 2-amino-2-methylpropanol (AMP). In this study, several key parameters were analyzed to understand the behavior of the aqueous DIPA/AMP system for CO capture. Including DIPA (9-21 wt%), AMP (9-21 wt%), temperature (323.
View Article and Find Full Text PDFDextran stabilised hematite: a sustainable anode in aqueous electrolytes.
Nanoscale
January 2025
Department of Materials Science and Engineering, University of Crete, 700 13 Heraklion, Crete, Greece.
During the last decades, the use of innovative hybrid materials in energy storage devices has led to notable advances in the field. However, further enhancement of their electrochemical performance faces significant challenges nowadays, imposed by the materials used in the electrodes and the electrolyte. Such problems include the high solubility of both the organic and the inorganic anode components in the electrolyte as well as the limited intrinsic electronic conductivity and substantial volume variation of the materials during cycling.
View Article and Find Full Text PDFDevelopment of Solid Self-Nanoemulsifying Drug Delivery System of Rhein to Improve Biopharmaceutical Performance: Physiochemical Characterization, and Pharmacokinetic Evaluation.
Int J Nanomedicine
January 2025
Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Arar, Saudi Arabia.
Introduction: Rhein, a natural bioactive lipophilic compound with numerous pharmacological activities, faces limitations in clinical application due to poor aqueous solubility and low bioavailability. Thus, this study aimed to develop a rhein-loaded self-nano emulsifying drug delivery system (RL-SNEDDS) to improve solubility and bioavailability.
Methods: The RL-SNEDDS was prepared by aqueous titration method with eucalyptus oil (oil phase), tween 80 (surfactant), and PEG 400 (co-surfactant) and optimization was performed by 3 factorial design.
Effect of solvent on the development of Poly(2-ethyl-2-oxazoline) nanofibrous scaffolds using electrospinning technique for biomedical applications.
Heliyon
January 2025
Department of Chemistry, Karnatak University Dharwad, Dharwad, 580003, India.
The selection of a biomaterial plays a very important role for the development of scaffolds for biomedical applications. Amidst, the development of nanofibrous scaffolds through electrospinning technique by selecting a suitable polymer is of more importance. Poly (2-ethyl-2-oxazoline) (PEOX) is one among the selected polymers that can be employed for electrospinning for the development of scaffolds for biomedical applications.
View Article and Find Full Text PDFFluorescence tunable carbon dots for nuclear dynamics and gastrointestinal imaging in live zebrafish and their toxicity evaluation by cardio-craniofacial disfunction assessment.
Nanoscale
January 2025
Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai-400085, India.
Sub-cellular organelle anomalies are frequently observed in diseases such as cancer. Early and precise diagnosis of these alterations can be crucial for patient outcomes. However, current diagnostic tools using conventional organic dyes or metal quantum dots face limitations, including poor biocompatibility, stringent storage conditions, limited solubility in aqueous media, and slow staining speeds.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!