Recent Advances in Molecular Mechanisms of Nucleoside Antivirals

Current Issues in Molecular Biology, Год журнала: 2023, Номер 45(8), С. 6851 - 6879

Опубликована: Авг. 17, 2023

The search for new drugs has been greatly accelerated by the emergence of viruses and drug-resistant strains known pathogens. Nucleoside analogues (NAs) are a prospective class antivirals due to safety profiles, which important rapid repurposing in fight against emerging Recent improvements research methods have revealed unexpected details mechanisms action NAs that can pave way approaches further development effective drugs. This review accounts advanced techniques viral polymerase targeting, host enzyme targeting approaches, prodrug-based strategies antiviral NAs.

Язык: Английский

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Purine nucleoside antibiotics: recent synthetic advances harnessing chemistry and biology

Natural Product Reports, Год журнала: 2024, Номер 41(6), С. 873 - 884

Опубликована: Янв. 1, 2024

This Highlight offers a perspective on recent strategies for synthesising purine nucleoside antibiotics, an untapped source of natural products developing novel antimicrobial agents.

Язык: Английский

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Recent advances in genome mining and synthetic biology for discovery and biosynthesis of natural products

Critical Reviews in Biotechnology, Год журнала: 2024, Номер unknown, С. 1 - 21

Опубликована: Авг. 12, 2024

Natural products have long served as critical raw materials in chemical and pharmaceutical manufacturing, primarily which can provide superior scaffolds or intermediates for drug discovery development. Over the last century, natural contributed to more than a third of therapeutic production. However, traditional methods producing drugs from become less efficient expensive over past few decades. The combined utilization genome mining synthetic biology based on sequencing, bioinformatics tools, big data analytics, genetic engineering, metabolic systems promises counter this trend. Here, we reviewed recent (2020–2023) examples used resolve challenges production products, such variety, poor efficiency, low yield. Additionally, emerging design principles, building strategies its application prospects NPs synthesis also been discussed.

Язык: Английский

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Discovery of C-Linked Nucleoside Analogues with Antiviral Activity against SARS-CoV-2

ACS Infectious Diseases, Год журнала: 2024, Номер 10(5), С. 1780 - 1792

Опубликована: Апрель 23, 2024

The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir molnupiravir, but a need still exists for therapies improved potency systemic exposure oral dosing, better metabolic stability, reduced resistance toxicity risks. Herein, we summarize our toward identifying that led to nucleoside 10e 10n, which showed favorable pan-coronavirus activity in cell-infection screens, were metabolized active triphosphate nucleotides cell-incubation studies, demonstrated target (nsp12) engagement biochemical assays.

Язык: Английский

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Synthesis of gem-Difluorinated 2,3-Dihydrobenzofurans Using Freon-22 via [4 + 1] Annulation of Difluorocarbene and Antitumor Activity Evaluation

Organic Letters, Год журнала: 2024, Номер 26(6), С. 1212 - 1217

Опубликована: Фев. 1, 2024

As an inexpensive industrial chemical, chlorodifluoromethane (Freon-22), despite its relatively low reactivity, can serve as a practical CF

Язык: Английский

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Recent advances in stereoselective synthesis of non-classical glycosides

Tetrahedron Chem, Год журнала: 2024, Номер 9, С. 100068 - 100068

Опубликована: Фев. 24, 2024

Язык: Английский

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Modular Synthesis and Cytotoxicity Evaluation of Dragocins A—C and Their Analogues: Discovery of a Potential Anticancer Agent

Chinese Journal of Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Comprehensive Summary Dragocins A—C are structurally unique marine natural products featuring an uncommon tri‐oxa‐tricyclic[6.2.1]undecane moiety. However, their extremely low abundance has hindered extensive screening of bioactivities. We hereby describe efficient and modular approach to synthesizing dragocins analogues using commercially available inexpensive anisomycin D‐ribosyl thioglycoside derivative as the starting materials. A key feature our synthesis is construction skeleton. This challenging architecture achieved by stereocontrolled formation β‐ribofuranosidic bond DDQ (2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone)‐promoted intramolecular cross‐dehydrogenative etherification at benzylic position. Our also characterized successful installation a chlorine atom methoxy group tertiary C‐4' position via late‐stage silver‐catalyzed decarboxylative chlorination reaction electrophilic enol intermediate. Cytotoxicity evaluations synthesized compounds revealed demethyl dragocin A, N ‐demethylated potential anticancer candidate due its strong cytotoxicity against A549 lung, HCT116 colorectal MCF7 breast cancer cell lines. work demonstrated preliminary structure‐activity relationship this compound, setting solid foundation for developing novel candidates.

Язык: Английский

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Exploration of 4′-fluoro fleximer nucleoside analogues as potential broad-spectrum antiviral agents

Bioorganic & Medicinal Chemistry, Год журнала: 2025, Номер unknown, С. 118243 - 118243

Опубликована: Май 1, 2025

Язык: Английский

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Cation-π-interaction-facilitated, self-photocatalyzed and regioselective perfluoroalkylation of 3-aza-1,5-dienes

Molecular Catalysis, Год журнала: 2023, Номер 547, С. 113360 - 113360

Опубликована: Июль 7, 2023

Язык: Английский

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Photoinduced Regioselective Perfluoroalkylation/Cyclization Cascade of 3‐Aza‐1,5‐Dienes: Access to Pentasubstituted 3‐Perfluoroalkyl‐1,3‐Dihydropyrrol‐2‐Ones

European Journal of Organic Chemistry, Год журнала: 2023, Номер 26(31)

Опубликована: Июль 12, 2023

Abstract A visible light‐induced perfluoroalkylative cyclization of 3‐aza‐1,5‐dienes leading to pentasubstituted 1,3‐dihydropyrrole‐2‐ones is presented. The reaction regiospecific, for the radical adds across acrylamido moiety, whereas enaminic double bond functions as a built‐in trap. It could be carried out on 2‐gram scale, and sunlight usable light source. Other virtues protocol include short time, low catalyst loading, mild conditions broad substrate scope.

Язык: Английский

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