Synthesis, anti-inflammatory activity, and conformational relationship studies of chromone derivatives incorporating amide groups

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2023, Номер 96, С. 129539 - 129539

Опубликована: Ноя. 1, 2023

Язык: Английский

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Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 264, С. 115979 - 115979

Опубликована: Ноя. 25, 2023

Язык: Английский

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Mask and Release Strategy‐Enabled Diversity‐Oriented Synthesis for DNA‐Encoded Library

Advanced Science, Год журнала: 2023, Номер 11(6)

Опубликована: Дек. 3, 2023

Abstract An ideal DNA‐encoded library (DEL) selection requires the to consist of diverse core skeletons and cover chemical space as much possible. However, lack efficient on‐DNA synthetic approaches toward has greatly restricted diversity DEL. To mitigate this issue, work disclosed a “Mask & Release” strategy streamline challenging skeleton synthesis. N ‐phenoxyacetamide is used masked phenol versatile directing group mediate diversified DNA‐compatible C‐H functionalization, introducing 1st‐dimensional at defined site, simultaneously releasing functionality, which can facilitate introduction 2nd diversity. This not only provides set syntheses DNA‐conjugated drug‐like such ortho ‐alkenyl/sulfiliminyl/cyclopropyl phenol, benzofuran, dihydrobenzofuran but also paradigm for method development.

Язык: Английский

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Synthesis, molecular docking analysis and in vitro evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents

RSC Advances, Год журнала: 2024, Номер 14(3), С. 1838 - 1853

Опубликована: Янв. 1, 2024

Two different synthetic approaches to novel heterocyclic hybrid compounds of 4-azapodophyllotoxin were investigated. The obtained products characterized by infrared spectroscopy, nuclear magnetic resonance and high-resolution mass spectrometry. MTT protocol was then performed examine the cytotoxic activity these against KB, HepG2, A549, MCF7, Hek-293 cell lines. assessment indicated that all displayed moderate high cytotoxicity tested cancer most active compound 13k containing 2-methoxypyridin-4-yl group exhibited selective HepG2 lines with IC50 values ranging from 0.23 0.27 μM, which between 5- 10-fold more potent than positive control ellipticine. Compounds 13a (HetAr = thiophen-3-yl) 13d 5-bromofuran-2-yl) selectivity for A549 when compared other low toxicity normal line. Molecular docking study conducted evaluate interaction new synthesized colchicine-binding-site tubulin. Besides that, physicochemical pharmacokinetic properties 13h,k predicted.

Язык: Английский

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Thiophene-fused γ-lactams inhibit the SARS-CoV-2 main protease via reversible covalent acylation

Chemical Science, Год журнала: 2024, Номер 15(20), С. 7667 - 7678

Опубликована: Янв. 1, 2024

Thiophene-fused γ-lactams are reversible covalent inhibitors of the SARS-CoV-2 main protease, a nucleophilic cysteine enzyme. γ-Lactams can inhibit enzymes by S -acylation as well serine O -acylation.

Язык: Английский

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Iodine catalyzed synthesis of imidazo[1,2-a]pyrazine and imidazo[1,2-a]pyridine derivatives and their anticancer activity

RSC Advances, Год журнала: 2023, Номер 13(51), С. 36439 - 36454

Опубликована: Янв. 1, 2023

Herein, we present the iodine catalyzed an efficient synthesis of imidazo[1,2- a ]pyrazine and pyridine derivatives studied their anticancer activities against in vitro cancer cell lines namely, Hep-2, HepG2, MCF-7, A375.

Язык: Английский

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Exploiting high-energy hydration sites for the discovery of potent peptide aldehyde inhibitors of the SARS-CoV-2 main protease with cellular antiviral activity

Bioorganic & Medicinal Chemistry, Год журнала: 2024, Номер 103, С. 117577 - 117577

Опубликована: Янв. 5, 2024

Small-molecule antivirals that prevent the replication of SARS-CoV-2 virus by blocking enzymatic activity its main protease (Mpro) are and will be a tenet pandemic preparedness. However, peptidic nature such compounds often precludes design within favorable physical property ranges, limiting cellular activity. Here we describe discovery peptide aldehyde Mpro inhibitors with potent antiviral This structure-activity relationship (SAR) exploration was guided use calculated hydration site thermodynamic maps (WaterMap) to drive potency via displacement waters from high-energy sites. Thousands diverse were designed target these sites then prioritized for synthesis physics- structure-based Free-Energy Perturbation (FEP+) simulations, which accurately predicted biochemical potencies. approach ultimately led rapid lead unique SAR exhibited excellent pan-coronavirus coverage.

Язык: Английский

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The Third CACHE Challenge – Finding Ligands Targeting the Macrodomain of SARS-CoV-2 NSP3 Using AI-inspired and Knowledge-Based Approaches.

Опубликована: Фев. 12, 2024

The SARS-CoV-2 virus contains a host of nonstructural proteins (NSPs) that contribute to its structure and viral function. Among them is the protein 3 (NSP3), which macrodomain (Mac1) interferes with antiviral adenosine diphosphate (ADP)-ribosylation signaling. Catalytic mutations in Mac1 render viruses nonpathogenic, making this enzyme promising target for development. For reason, third CACHE challenge focused on identifying binders domain NSP3 development novel antivirals against SARS-CoV-2. To end, we used available structural data complex known fragment as starting points ligand discovery; our efforts were primarily sub-sites ADP binding site macrodomain. Then, using Artificial intelligence (AI)-guided knowledge-based merging expansion approaches, generated molecules would serve templates identify highly similar compounds Enamine REAL database be commercially available. Our design yielded library 12,800 molecules, was docked program FITTED representative crystal NSP3. We ranked predicted poses based docking score, followed by visual pose analysis best 200 compounds. finally selected proposed 150 testing, further shortlisting yield final list 107 molecules. 91 purchased from are being tested at Structural Genomics Consortium (SGC). approach findings will open science efforts, aim continue engage scientific community.

Язык: Английский

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Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein

Free Radical Biology and Medicine, Год журнала: 2024, Номер 220, С. 167 - 178

Опубликована: Май 6, 2024

Язык: Английский

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Anticoronavirus activity of rhizome of Dryopteris crassirhizoma via multistage targeting of virus entry and viral proteases, Mpro and PLpro

Journal of Ethnopharmacology, Год журнала: 2024, Номер 333, С. 118490 - 118490

Опубликована: Июнь 25, 2024

The rhizome of Dryopteris crassirhizoma Nakai (Dryopteridaceae, RDC), a traditional East Asian herbal medicine, possesses broad spectrum medicinal properties, including anti-inflammatory, anticancer, antibacterial, and antiviral activities.

Язык: Английский

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