It is advocated that kinetic and thermodynamic profiling of bioactive compounds should be incorporated and utilized as complementary tools for hit and lead optimizations in drug discovery. To assess their applications in the EED hit-to-lead optimization process, large amount of thermodynamic and kinetic data were collected and analyzed via isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR), respectively. Slower dissociation rates (k) of the lead compounds were observed as the program progressed. Analysis of the kinetic data indicated that compound cellular activity correlated with both K and k. Our analysis revealed that ITC data should be interpreted in the context of chiral purity of the compounds. The thermodynamic signatures of the EED aminopyrrolidine compounds were found to be mainly enthalpy driven with improved enthalpic contributions as the program progressed. Our study also demonstrated that significant challenges still exist in utilizing kinetic and thermodynamic parameters for hit selection.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jmedchem.7b00576 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nickel removal from synthetic wastewater by novel zeolite-doped magnesium- iron- and zinc-oxide nanocomposites by hydrothermal-calcination technique.
Sci Rep
December 2024
Qatar Environment and Energy Research Institute (QEERI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, 34110, Qatar.
This study aims to modify raw zeolite with metal oxide nanocomposites to remove nickel (Ni) ions from synthetic wastewater. Novel zeolite-doped magnesium oxide (MgO), iron oxide (FeO), and zinc oxide (ZnO) nanocomposites were synthesized by hydrothermal-calcination methods. The novel zeolite-doped metal oxide nanocomposites were used as adsorbents to remove Ni (II) ions from synthetic wastewater.
View Article and Find Full Text PDFSelective O/N Separation Using Grazyne Membranes: A Computational Approach Combining Density Functional Theory and Molecular Dynamics.
Nanomaterials (Basel)
December 2024
Departament de Ciència de Materials i Química Física, Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, C/Martí i Franquès 1-11, 08028 Barcelona, Spain.
The separation of oxygen (O) and nitrogen (N) from air is a process of utmost importance nowadays, as both species are vital for numerous fundamental processes essential for our development. Membranes designed for their selective molecule separation have become the materials of choice for researchers, primarily due to their ease of use. The present study proposes grazynes, 2D carbon-based materials consisting of and C atoms, as suitable membranes for separating O and N from air.
View Article and Find Full Text PDFEnvironmentally Friendly Nanoporous Polymeric Gels for Sustainable Wastewater Treatment.
Gels
November 2024
Department of Chemistry, Helwan University, Ain-Helwan 11795, Egypt.
Environmentally friendly nanoporous gels are tailor-designed and employed in the adsorption of toxic organic pollutants in wastewater. To ensure the maximum adsorption of the contaminant molecules by the gels, molecular modeling techniques were used to evaluate the binding affinity between the toxic organic contaminants such as methylene blue (MB) and Congo red (CR) and various biopolymers. To generate nanopores in the matrix of the polymeric gels, salt crystals were used as porogen.
View Article and Find Full Text PDFComputational Insights into Hydrogen Atom Transfer Mediators in C-H Activation Catalysis of Nonheme Fe(IV)O Complexes.
J Phys Chem B
December 2024
Department of Chemistry and Biochemistry, Thapar Institute of Engineering and Technology, Patiala 147001, Punjab, India.
This study presents a detailed density functional theory (DFT) investigation into the mechanism and energetics of C-H activations catalyzed by bioinspired Fe(IV)O complexes, particularly in the presence of -hydroxy mediators. The findings show that these mediators significantly enhance the reactivity of the iron-oxo complex. The study examines three substrates with varying bond dissociation energies─ethylbenzene, cyclohexane, and cyclohexadiene─alongside the [Fe(IV)O(N4Py)] complex.
View Article and Find Full Text PDFA Quantum Chemistry Insight into the Potential Role of the Singlet Oxygen-Acetone System as a Source for Production of Stable Secondary Organic Aerosols through a Multiwell Multipath Reaction.
J Phys Chem A
December 2024
Department of Chemistry, University of Zanjan, PO Box 38791-45371 Zanjan, Iran.
The high abundance of acetone ((CH)C═O), which makes it a good candidate for oxygenated molecules, and the high reactivity of oxygen atoms in the first excited state O(D) are two well-known facts in the chemistry of the atmosphere. In this research, we prove that the singlet oxygen and acetone system is capable of proceeding through multiwell multipath reactions, leading to the production of several organic aerosols. Hence, the nature of species released by the (CH)C═O + O(D) reaction to air can be clarified by profound attention to the possible routes.
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!