Syntheses, reactivity, and biological applications of coumarins

Frontiers in Chemistry, Год журнала: 2024, Номер 12

Опубликована: Фев. 19, 2024

This comprehensive review, covering 2021-2023, explores the multifaceted chemical and pharmacological potential of coumarins, emphasizing their significance as versatile natural derivatives in medicinal chemistry. The synthesis functionalization coumarins have advanced with innovative strategies. enabled incorporation diverse functional fragments or construction supplementary cyclic architectures, thereby biological physico-chemical properties compounds obtained were enhanced. unique structure coumarine facilitates binding to various targets through hydrophobic interactions pi-stacking, hydrogen bonding, dipole-dipole interactions. Therefore, this important scaffold exhibits promising applications uncountable fields chemistry (e.g., neurodegenerative diseases, cancer, inflammation).

Язык: Английский

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Recent Advances in SARS-CoV-2 Main Protease Inhibitors: From Nirmatrelvir to Future Perspectives

Biomolecules, Год журнала: 2023, Номер 13(9), С. 1339 - 1339

Опубликована: Сен. 2, 2023

The main protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered highly conserved viral target. Disruption catalytic activity Mpro produces detrimental effect on course infection, making this target one most attractive for treatment COVID-19. current success SARS-CoV-2 inhibitor Nirmatrelvir, first oral drug forms COVID-19, has further focused attention researchers important target, search new inhibitors thriving exciting field development antiviral drugs active against related coronaviruses.

Язык: Английский

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The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19

Pharmaceutics, Год журнала: 2024, Номер 16(2), С. 217 - 217

Опубликована: Фев. 2, 2024

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented an enormous challenge to health care systems and medicine. As a result of global research efforts aimed at preventing effectively treating SARS-CoV-2 infection, vaccines with fundamentally new mechanisms action some small-molecule antiviral drugs targeting key proteins in the viral cycle have been developed. most effective drug approved date for treatment is PaxlovidTM, which combination two protease inhibitors, nirmatrelvir ritonavir. Nirmatrelvir reversible covalent peptidomimetic inhibitor main (Mpro) SARS-CoV-2, enzyme plays crucial role reproduction. In this combination, ritonavir serves as pharmacokinetic enhancer, it irreversibly inhibits cytochrome CYP3A4 responsible rapid metabolism nirmatrelvir, thereby increasing half-life bioavailability nirmatrelvir. tutorial review, we summarize development pharmaceutical chemistry aspects Paxlovid, covering evolution warhead design, synthesis mechanism well its inhibition mechanism. efficacy Paxlovid novel virus mutants also overviewed.

Язык: Английский

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Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

Molecules, Год журнала: 2023, Номер 28(16), С. 5969 - 5969

Опубликована: Авг. 9, 2023

Tyrosinase plays crucial roles in mediating the production of melanin pigment; thus, its inhibitors could be useful preventing melanin-related diseases. To find potential tyrosinase inhibitors, a series cinnamic acid-eugenol esters (c1~c29) was synthesized and their chemical structures were confirmed by 1H NMR, 13C HRMS, FT-IR, respectively. The biological evaluation results showed that all compounds c1~c29 exhibited definite inhibitory activity; especially, compound c27 strongest inhibitor (IC50: 3.07 ± 0.26 μM), being ~4.6-fold stronger than positive control, kojic acid 14.15 0.46 μM). Inhibition kinetic studies validated as reversible mixed-type against tyrosinase. Three-dimensional fluorescence circular dichroism (CD) spectra indicated change conformation secondary structure Fluorescence-quenching quenched static manner with one binding site. Molecular docking also revealed interactions between Therefore, esters, especially c27, used lead to inhibitors.

Язык: Английский

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Recent Advances on SARS-CoV-2 Mpro Inhibitors: From Nirmatrelvir to Future Perspectives

Опубликована: Авг. 2, 2023

The Main Protease (Mpro) plays a pivotal role in the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is considered highly conserved viral target. Disruption catalytic activity Mpro produces detrimental effect on course infection, making this target one most attractive for treatment COVID-19. current success SARS-CoV-2 inhibitor Nirmatrelvir, first oral drug forms COVID-19, has further focused attention researchers important target, search new inhibitors thriving exciting field development antiviral drugs active against related coronaviruses.

Язык: Английский

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Cinnamyl Alcohol Attenuates Adipogenesis in 3T3-L1 Cells by Arresting the Cell Cycle

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(2), С. 693 - 693

Опубликована: Янв. 5, 2024

Cinnamyl alcohol (CA) is an aromatic compound found in several plant-based resources and has been shown to exert anti-inflammatory anti-microbial activities. However, the anti-adipogenic mechanism of CA not sufficiently studied. The present study aimed investigate effect on regulation adipogenesis. As evidenced by Oil Red O staining, Western blotting, real-time PCR (RT-PCR) analyses, treatment (6.25-25 μM) for 8 d significantly inhibited lipid accumulation a concentration-dependent manner downregulated adipogenesis-related markers (peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), fatty acid binding 4 (FABP4), adiponectin, synthase (FAS)) 3-isobutyl-1-methylxanthine, dexamethasone, insulin(MDI)-treated 3T3-L1 adipocytes. In particular, among various differentiation stages, early stage adipogenesis was critical inhibitory CA. Cell cycle analysis using flow cytometry blotting showed that effectively MDI-induced initiation mitotic clonal expansion (MCE) arresting cell G

Язык: Английский

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A Green Approach to Nucleophilic Aromatic Substitutions of Nicotinic Esters in Cyrene

European Journal of Organic Chemistry, Год журнала: 2024, Номер 27(15)

Опубликована: Янв. 29, 2024

Abstract The green solvent Cyrene TM has emerged as a valuable substitute for conventional polar aprotic organic solvents such DMF, DMSO and NMP (renowned their toxicity environmental concerns). However, in the presence of bases, is prone to polymerization, thus potentially incompatible with reactions where base needed generate reactive nucleophiles. In this study, we developed an efficient synthetic strategy nucleophilic aromatic substitutions nicotinic esters Cyrene. success protocol relies on very short reaction time (only 15 minutes) which prevents polymerization from occurring. Indeed, not only outperformed typical DMF DMSO, but also, being highly soluble water, allowed easy purification desired products by simple precipitation upon addition ice‐water.

Язык: Английский

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Discovery of Indole–Thiourea Derivatives as Tyrosinase Inhibitors: Synthesis, Biological Evaluation, Kinetic Studies, and In Silico Analysis

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9636 - 9636

Опубликована: Сен. 5, 2024

Tyrosinase, a key enzyme in melanin synthesis, represents crucial therapeutic target for hyperpigmentation disorders due to excessive production. This study aimed design and evaluate series of indole–thiourea derivatives by conjugating thiosemicarbazones with strong tyrosinase inhibitory activity indole. Among these derivatives, compound 4b demonstrated an IC50 5.9 ± 2.47 μM, outperforming kojic acid (IC50 = 16.4 3.53 μM). Kinetic studies using Lineweaver–Burk plots confirmed competitive inhibition 4b. Its favorable ADMET drug-likeness properties make promising candidate reduced risk toxicity. Molecular docking revealed that the compounds bind strongly mushroom (mTYR) human tyrosinase-related protein 1 (TYRP1), showing superior binding energies −7.0 kcal/mol −6.5 surpassing both tropolone. dynamics simulations stability mTYR−4b complex low RMSD RMSF consistent Rg SASA values. Persistent hydrogen bonds mTYR, along Gibbs free energy MM/PBSA calculations (−19.37 kcal/mol), further support stable protein–ligand interactions. Overall, pharmacokinetics, highlighting its potential treating pigmentary disorders.

Язык: Английский

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Research Progress on the Structure and Function, Immune Escape Mechanism, Antiviral Drug Development Methods, and Clinical Use of SARS-CoV-2 Mpro

Molecules, Год журнала: 2025, Номер 30(2), С. 351 - 351

Опубликована: Янв. 16, 2025

The three-year COVID-19 pandemic ‘has’ caused a wide range of medical, social, political, and financial implications. Since the end 2020, various mutations variations in SARS-CoV-2 strains, along with immune escape phenomenon, have emerged. There is an urgent need to identify relatively stable target for development universal vaccines drugs that can effectively combat both strains their mutants. Currently, main focus treating lies disrupting virus’s life cycle. protease (Mpro) closely associated virus replication maturation plays crucial role early stages infection. Consequently, it has become important SARS-CoV-2-specific drugs. This review summarizes recent research progress on novel coronavirus’s proteases, including pivotal Mpro cycle, structure catalytic mechanism Mpro, self-maturation escape, current methods developing antiviral targeting key successfully entered clinical trials. aim provide researchers involved systematic comprehensive information.

Язык: Английский

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Design, synthesis and in vitro validation of bivalent binders of SARS-CoV-2 spike protein: Obeticholic, betulinic and glycyrrhetinic acids as building blocks

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер 121, С. 118124 - 118124

Опубликована: Фев. 18, 2025

Язык: Английский

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