Fluorine-a small magic bullet atom in the drug development: perspective to FDA approved and COVID-19 recommended drugs

Chemical Papers, Journal Year: 2023, Volume and Issue: 77(8), P. 4085 - 4106

Published: April 13, 2023

Language: Английский

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The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(20), P. 15503 - 15602

Published: May 25, 2022

Fluorinated carbohydrates have found many applications in the glycosciences. Typically, these contain fluorination at a single position. There are not involving polyfluorinated carbohydrates, here defined as monosaccharides which more than one carbon has least fluorine substituent directly attached to it, with notable exception of their use mechanism-based inhibitors. The increasing attention carbohydrate physical properties, especially around lipophilicity, resulted surge interest for this class compounds. This review covers considerable body work toward synthesis hexoses, pentoses, ketosugars, and aminosugars including sialic acids nucleosides. An overview current state art glycosidation is also provided.

Language: Английский

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4′-Fluoro-nucleosides and nucleotides: from nucleocidin to an emerging class of therapeutics

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 52(1), P. 248 - 276

Published: Dec. 6, 2022

The history and development of 4'-fluoro-nucleosides is discussed in this review. This a class nucleosides which have their origin the discovery rare fluorine containing natural product nucleocidin. Nucleocidin contains atom located at 4'-position its ribose ring. From early isolation as an unexpected product, to total synthesis bioactivity assessment, nucleocidin has played role inspiring exploration privileged motif for nucleoside-based therapeutics.

Language: Английский

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Exploring chemical space, scaffold diversity, and activity landscape of spleen tyrosine kinase active inhibitors

SAR and QSAR in environmental research, Journal Year: 2024, Volume and Issue: 35(4), P. 325 - 342

Published: April 2, 2024

This study aims to comprehensively characterize 576 inhibitors targeting Spleen Tyrosine Kinase (SYK), a non-receptor tyrosine kinase primarily found in haematopoietic cells, with significant relevance B-cell receptor function. The objective is gain insights into the structural requirements essential for potent activity, implications various therapeutic applications. Through chemoinformatic analyses, we focus on exploring chemical space, scaffold diversity, and structure-activity relationships (SAR). By leveraging ECFP4 MACCS fingerprints, elucidate relationship between compounds visualize network using RDKit NetworkX platforms. Additionally, compound clustering visualization of associated space aid understanding overall diversity. outcomes include identifying consensus diversity patterns assess global Furthermore, incorporating pairwise activity differences enhances landscape visualization, revealing heterogeneous SAR patterns. dataset analysed this work has three cliff generators, CHEMBL3415598, CHEMBL4780257, CHEMBL3265037, high affinity SYK are very similar analogues reasonable potency differences. Overall, provides critical analysis inhibitors, uncovering potential scaffolds moieties crucial their thereby advancing potential.

Language: Английский

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Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties

Molecules, Journal Year: 2024, Volume and Issue: 29(10), P. 2390 - 2390

Published: May 19, 2024

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral anticancer activity. insertion of a fluorine atom, either base or sugar nucleos(t)ides, alters its electronic steric parameters transforms lipophilicity, pharmacodynamic, pharmacokinetic properties these moieties. atom restricts oxidative metabolism provides enzymatic metabolic stability towards glycosidic bond nucleos(t)ide. incorporation also demonstrates additional hydrogen bonding interactions receptors with enhanced biological profiles. present article discusses synthetic methodology activities FDA-approved ongoing fluoro-containing nucleos(t)ide drug candidates

Language: Английский

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Chemical Space of Fluorinated Nucleosides/Nucleotides in Biomedical Research and Anticancer Drug Discovery

Chemistry, Journal Year: 2025, Volume and Issue: 7(1), P. 7 - 7

Published: Jan. 13, 2025

Fluorinated nucleos(t)ide drugs have proven to be successful chemotherapeutic agents in treating various cancers. The Food and Drug Administration (FDA) has approved several that fit within the fluorinated nucleoside pharmacophore, many more are either preclinical development or clinical trials. addition of fluorine atoms nucleos(t)ides improves metabolic stability glycosidic bond and, certain instances, facilitates additional interactions nucleons(t)ides with receptors. insertion on sugar base proved enhance lipophilicity, pharmacokinetic, pharmacodynamic properties. Overall, atom feeds diverse advantages biological profile analogs by improving their drug-like properties therapeutic potential. This review article covers often-used fluorinating reagents chemistry, significance [18F]-labeled nucleosides, synthesis anticancer activity FDA-approved fluoro-nucleos(t)ide drugs, as well candidates, which at stages agents.

Language: Английский

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The literature of heterocyclic chemistry, part XXII, 2022

Advances in heterocyclic chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Light‐ and Water‐Driven Nanoarchitectonics of Amphiphilic Azobenzene Derivatives: Photoswitching and Self‐Aggregation Dispersion Studies

ChemPhotoChem, Journal Year: 2025, Volume and Issue: unknown

Published: May 30, 2025

Herein, how aggregation‐dispersion behavior of fluorinated azobenzene derivatives 5 and 6 with an amphiphilic dodecaoctane substituent is affected by UV light irradiation water described. The influence fluorine substituents on their photophysical properties, photoswitching differences, aggregation in waterin‐ground trans excited cis ‐state studied. Their properties are investigated under the polar MeOH nonpolar solvent benzene it found that shows different as compared to both solvents. Further, check MeOH, a competing added. It observed MeOH–H 2 O solution (0.9‐1.5 mL), compounds show redshift decrease absorbance, fluorescence emission found. dynamic scattering opposite behavior, initially macromolecular aggregated state ‐states but addition disperses solution. However, uniform micromolecular features further after water. Scanning electron microscopy images suggest patterns change morphology when added IR, 1 H, 19 F NMR done understand site intermolecular interactions.

Language: Английский

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Chemical and photophysical studies on the interaction of reactive oxygen species with carbonylated diazo derivatives: Their chromogenic, fluorescent detection and mechanistic investigation

Dyes and Pigments, Journal Year: 2023, Volume and Issue: 216, P. 111317 - 111317

Published: April 12, 2023

Language: Английский

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Safety Assessment of a Nucleoside Analogue FNC (2’-deoxy-2’- β-fluoro-4’-azidocytidine ) in Balb/c Mice: Acute Toxicity Study

Asian Pacific Journal of Cancer Prevention, Journal Year: 2023, Volume and Issue: 24(6), P. 2157 - 2170

Published: June 1, 2023

Objectives: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2'-deoxy-2'-β-fluoro-4'-azidocytidine). showed potent anti-viral and anti-cancer activities approved drug for high-load HIV patients, despite, its being lacking. Materials Methods: OECD-423 guidelines were followed during this parameters divided four categories - behavioral parameters, physiological histopathological supplementary tests. included feeding, body weight, belly size, organ weight mice behavior. consisted blood, liver, kidney indicators. In hematoxylin eosin staining was performed analyse histological changes in organs after exposure. addition, tests conducted assess cellular viability, DNA fragmentation cytokine levels (IL-6 TNF-α) response FNC. Results: induced mice-to-mice interaction activities. Mice's size remained unchanged. Physiological blood that increased level WBC, RBC, Hb, neutrophils decreased % count lymphocytes. Liver enzymes SGOT (AST), ALP increased. renal function test (RFT) cholesterol significantly decreased. Histopathological analysis kidney, brain, heart, lungs, spleen no sign tissue damage at highest dose 25 mg/kg b.wt. Supplementary cell viability change footprint, through our recently developed dilution cum-trypan (DCT) assay, Annexin/PI. No or apoptosis observed DAPI AO/EtBr studies. Pro-inflammatory cytokines IL-6 TNF-α dose-dependent manner. Conclusion: This concluded is safe use though higher concentration shows slight toxicity.

Language: Английский

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