scholarly journals Synthesis and ADMET Study of Some 1, 8-Naphthyidine and Quinoline 3-Carboxylic Acid Derivatives

2021 ◽  
Vol 9 (11) ◽  
pp. 1932-1938
Author(s):  
Vinod Kumar Gurjar
Keyword(s):  
Carboxylic Acid ◽  
Virtual Screening ◽  
Heterocyclic Compound ◽  
Mechanism Of Action ◽  
In Silico ◽  
Heterocyclic Compounds ◽  
Analytical Techniques ◽  
Drug Resistant ◽  
Alternate Mechanism ◽  
Selection Of

Abstract: The extremely drug resistant may be a worldwide public ill health in recent years. Molecules with newer targets and an alternate mechanism of action is an urgent requirement of improvement of latest drugs. The utilization of heterocyclic compounds has been increased dramatically over the last 70 years due to their wide selection of technical applications and their favorable environmental and toxicological properties The 1,8-naphthyridine and quinoline 3-carboxylic acid derivatives that we'll manufacture during this method will change the potency and specificity of fluoroquinolones. Taking under consideration the findings, the goal is to style and manufacture 1, 8-naphthyridine and quinoline 3-carboxylic acid derivatives. The synthesized compounds are going to be characterized using multiple analytical techniques, virtual screening, and in-silico ADME/T prediction. Keywords: 1, 8-Naphthyridine, Quinoline, ADMET, Heterocyclic Compound

scholarly journals Characterization of Phenolic Acid Antimicrobial and Antioxidant Structure–Property Relationships

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 419 ◽  
Author(s):  
Jingyi Liu ◽  
Changling Du ◽  
Henry T. Beaman ◽  
Mary Beth B. Monroe
Keyword(s):  
Carboxylic Acid ◽  
Antioxidant Properties ◽  
Antimicrobial Properties ◽  
Acid Group ◽  
Drug Resistant ◽  
Structure Property ◽  
Carboxylic Acid Group ◽  
Structure Property Relationships ◽  
Methoxy Groups ◽  
Selection Of

Plant-derived phenolic acids (PAs) are small molecules with antimicrobial, antioxidant, anti-inflammatory, and pro-coagulant properties. Their chemistry enables facile potential incorporation into biomaterial scaffolds to provide naturally-derived functionalities that could improve healing outcomes. While PAs have been previously characterized, their structure-property relationships in terms of antioxidant and antimicrobial properties are not well-understood, particularly in the context of their use in medical applications. To that end, a library of PAs with varied pendant groups was characterized here. It was found that increasing the number of radical-scavenging hydroxyl and methoxy groups on PAs increased antioxidant properties. All PAs showed some antimicrobial activity against the selected bacteria strains (Escherichia coli, Staphylococcus epidermidis (native and drug-resistant), and Staphylococcus aureus (native and drug-resistant)) at concentrations that are feasible for incorporation into polymeric biomaterials. In general, a trend of slightly decreased antimicrobial efficacy with increased number of pendant hydroxyl and methoxy groups was observed. The carboxylic acid group of a selection of PAs was modified with a polyurethane monomer analog. Modification did not greatly affect antioxidant or antimicrobial properties in comparison to unmodified controls, indicating that the carboxylic acid group of PAs can be altered without losing functionality. These results could be utilized for rational selection of phenolic moieties for use as therapeutics on their own or as part of a biomaterial scaffold with desired healing outcomes.

scholarly journals QSAR-Based Virtual Screening of Natural Products Database for Identification of Potent Antimalarial Hits

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 459
Author(s):  
Letícia Tiburcio Ferreira ◽  
Joyce V. B. Borba ◽  
José Teófilo Moreira-Filho ◽  
Aline Rimoldi ◽  
Carolina Horta Andrade ◽  
...  
Keyword(s):  
Natural Products ◽  
Virtual Screening ◽  
Low Income ◽  
In Silico ◽  
Biologically Active ◽  
Drug Resistant ◽  
Quantitative Structure ◽  
Physiologically Based Pharmacokinetic ◽  
Physiologically Based

With about 400,000 annual deaths worldwide, malaria remains a public health burden in tropical and subtropical areas, especially in low-income countries. Selection of drug-resistant Plasmodium strains has driven the need to explore novel antimalarial compounds with diverse modes of action. In this context, biodiversity has been widely exploited as a resourceful channel of biologically active compounds, as exemplified by antimalarial drugs such as quinine and artemisinin, derived from natural products. Thus, combining a natural product library and quantitative structure–activity relationship (QSAR)-based virtual screening, we have prioritized genuine and derivative natural compounds with potential antimalarial activity prior to in vitro testing. Experimental validation against cultured chloroquine-sensitive and multi-drug-resistant P. falciparum strains confirmed the potent and selective activity of two sesquiterpene lactones (LDT-597 and LDT-598) identified in silico. Quantitative structure–property relationship (QSPR) models predicted absorption, distribution, metabolism, and excretion (ADME) and physiologically based pharmacokinetic (PBPK) parameters for the most promising compound, showing that it presents good physiologically based pharmacokinetic properties both in rats and humans. Altogether, the in vitro parasite growth inhibition results obtained from in silico screened compounds encourage the use of virtual screening campaigns for identification of promising natural compound-based antimalarial molecules.

Discovery of New AKT1 Inhibitors by Combination of In silico Structure Based Virtual Screening Approaches and Biological Evaluations

2019 ◽  
Author(s):  
Filip Fratev ◽  
Denisse A. Gutierrez ◽  
Renato J. Aguilera ◽  
suman sirimulla
Keyword(s):  
Virtual Screening ◽  
Success Rate ◽  
Protein Interactions ◽  
In Silico ◽  
Biological Data ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Screening Protocol ◽  
Screening Approaches

AKT1 is emerging as a useful target for treating cancer. Herein, we discovered a new set of ligands that inhibit the AKT1, as shown by in vitro binding and cell line studies, using a newly designed virtual screening protocol that combines structure-based pharmacophore and docking screens. Taking together with the biological data, the combination of structure based pharamcophore and docking methods demonstrated reasonable success rate in identifying new inhibitors (60-70%) proving the success of aforementioned approach. A detail analysis of the ligand-protein interactions was performed explaining observed activities.<br>

Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently

2019 ◽  
Author(s):  
John Eaton ◽  
Richard A. Ruberto ◽  
Anneke Kramm ◽  
Vasanthi S. Viswanathan ◽  
Stuart Schreiber
Keyword(s):  
Molecular Mechanism ◽  
Mechanism Of Action ◽  
Therapeutic Target ◽  
Biologically Active ◽  
Drug Resistant ◽  
Nitrile Oxides ◽  
Molecular Mechanism Of Action

<div><div><div><p>GPX4 represents a promising yet difficult-to-drug therapeutic target for the treatment of, among others, drug-resistant cancers. While most GPX4 inhibitors rely on a chloroacetamide moiety to modify covalently the protein’s catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules has uncovered novel electrophilic warheads that bind and inhibit GPX4. Here we report our discovery that diacylfuroxans can act as masked nitrile oxides that inhibit GPX4 covalently. These observations illuminate a novel molecular mechanism of action for biologically active furoxans and also suggest that nitrile oxides may be uniquely suited to targeting GPX4.</p></div></div></div>

Modular, Stereocontrolled Cβ–H/Cα–C Activation of Alkyl Carboxylic Acids

2019 ◽  
Author(s):  
Ming Shang ◽  
Karla S. Feu ◽  
Julien C. Vantourout ◽  
Lisa M. Barton ◽  
Heather L. Osswald ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Heterocyclic Compounds ◽  
Cross Coupling ◽  
Building Blocks ◽  
Enantioselective Synthesis ◽  
Carbon Centers ◽  
Drug Candidates ◽  
Rapid Diversification ◽  
Directing Group ◽  
Compound Series

<div> <div> <div> <p>The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series. </p> </div> </div> </div>

Enalos Suite of Tools: Enhancing Cheminformatics and Nanoinfor - matics through KNIME

2020 ◽  
Vol 27 (38) ◽  
pp. 6523-6535 ◽  
Author(s):  
Antreas Afantitis ◽  
Andreas Tsoumanis ◽  
Georgia Melagraki
Keyword(s):  
Data Analysis ◽  
Virtual Screening ◽  
In Silico ◽  
Model Development ◽  
In Silico Analysis ◽  
Material Design ◽  
Efficient Solutions ◽  
Biological Data ◽  
Cost Efficient ◽  
Silico Analysis

Drug discovery as well as (nano)material design projects demand the in silico analysis of large datasets of compounds with their corresponding properties/activities, as well as the retrieval and virtual screening of more structures in an effort to identify new potent hits. This is a demanding procedure for which various tools must be combined with different input and output formats. To automate the data analysis required we have developed the necessary tools to facilitate a variety of important tasks to construct workflows that will simplify the handling, processing and modeling of cheminformatics data and will provide time and cost efficient solutions, reproducible and easier to maintain. We therefore develop and present a toolbox of >25 processing modules, Enalos+ nodes, that provide very useful operations within KNIME platform for users interested in the nanoinformatics and cheminformatics analysis of chemical and biological data. With a user-friendly interface, Enalos+ Nodes provide a broad range of important functionalities including data mining and retrieval from large available databases and tools for robust and predictive model development and validation. Enalos+ Nodes are available through KNIME as add-ins and offer valuable tools for extracting useful information and analyzing experimental and virtual screening results in a chem- or nano- informatics framework. On top of that, in an effort to: (i) allow big data analysis through Enalos+ KNIME nodes, (ii) accelerate time demanding computations performed within Enalos+ KNIME nodes and (iii) propose new time and cost efficient nodes integrated within Enalos+ toolbox we have investigated and verified the advantage of GPU calculations within the Enalos+ nodes. Demonstration data sets, tutorial and educational videos allow the user to easily apprehend the functions of the nodes that can be applied for in silico analysis of data.

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