Computer-aided design, synthesis, and biological evaluation of 4-chloro-N-(2-oxo-3-(2-pyridin-4-yl)hydrazineylidene)indolin-5yl)benzamide and 1-(4-bromobenzyl)-5-indoline-2,3-dione against SARS-CoV-2 spike/ACE2 DOI Creative Commons

Vanessa Asoh Shu,

Donatus Bekindaka Eni,

Mathieu Jules Mbenga Tjegbe

и другие.

The Microbe, Год журнала: 2024, Номер 4, С. 100143 - 100143

Опубликована: Авг. 15, 2024

The emergence of the severe acute respiratory syndrome 2 (SARS-CoV-2) as a global threat has driven urgent need for identification bioactive molecules capable controlling or completely eradicating this virus. Our group been investigating isatin hybrids that block binding human angiotensin-converting enzyme (ACE2) and viral spike protein. This work describes synthesis biological evaluation two derivatives (indol-2,3-dione) based on computational approach. Isatin, secondary metabolite tryptophan, used core structure is versatile favorable precursor privileged scaffold against complex. new compound scaffolds AVS-01 AVS-02 were designed by modifications at C-3 N-1 positions, respectively, according to various reagents available in our lab. Molecular docking compounds was explore their interactions with target protein shown article showed quite distinct glide scores (GScore = −3.657 −4.534 AVS-02, respectively). Several analogs synthesized tested quest find plausible further synthesis. While inhibition spike/ACE2 an IC50 value 8.8 µM, reference hopeaphenol inhibited interaction 0.3 µM. Compound rather no SARS-CoV-2 spike/host ACE2 > 32 An estimation free energy (ΔGbind), solvation (ΔGsolv) MM-GBSA calculations carried out re-evaluate affinity gain insights into observed activity non-activity. calculation ΔGbind −35.91 kcal/mol and-25.32 ΔGsolv 25.56 16.92 respectively. leads conclusion position indole-2,3-dione moiety favors blockage compared position. Analysis GScores, per-residue energies, energies van der Waals should favor towards

Язык: Английский

Synthesis, SARS-CoV-2 main protease inhibition, molecular docking and in silico ADME studies of furanochromene-quinoline hydrazone derivatives DOI

Blake M. Shellenberger,

Olivia N. Basile,

Joel Cassel

и другие.

Bioorganic & Medicinal Chemistry Letters, Год журнала: 2024, Номер 102, С. 129679 - 129679

Опубликована: Фев. 27, 2024

Язык: Английский

Процитировано

1
Chemical and Antiplasmodial Investigations on Eremophila-Derived Alkaloids and Semisynthetic Ether Analogues DOI
Chen Zhang, Kah Yean Lum, Jonathan M. White

и другие.

Journal of Natural Products, Год журнала: 2024, Номер 87(4), С. 849 - 854

Опубликована: Фев. 28, 2024

Microthecaline A (1), the known antiplasmodial quinoline serrulatane alkaloid from roots of Eremophila microtheca F. Muell. ex Benth. (Scrophulariaceae), was targeted for isolation and subsequent use in generation a semisynthetic ether library. large-scale extraction yielded previously undescribed microthecaline B (2), along with crystalline 1 that enabled first X-ray crystallographic analysis to be undertaken on this rare structure class. The diffraction supported absolute configuration assignment A, which originally assigned by ECD data analysis. (1) converted into 10 new derivatives (3–12) using diverse series commercially available alkyl halides. Chemical structures analogues were spectroscopic spectrometric analyses. Antiplasmodial evaluations 1–12 showed derivative 5 elicited most potent activity an IC50 value 7.2 μM against Plasmodium falciparum 3D7 (drug-sensitive) strain.

Язык: Английский

Процитировано

1
Metabolomic Analysis and Antiviral Screening of a Marine Algae Library Yield Jobosic Acid (2,5-Dimethyltetradecanoic Acid) as a Selective Inhibitor of SARS-CoV-2 DOI
Marie L. Matos-Hernández, Robert M. Samples, Grayce Dyer

и другие.

Journal of Natural Products, Год журнала: 2024, Номер 87(6), С. 1513 - 1520

Опубликована: Май 23, 2024

Current small-molecule-based SARS-CoV-2 treatments have limited global accessibility and pose the risk of inducing viral resistance. Therefore, a marine algae cyanobacteria extract library was screened for natural products that could inhibit two well-defined validated COVID-19 drug targets, disruption spike protein/ACE-2 interaction main protease (M

Язык: Английский

Процитировано

1
Drug repositioning identifies salvinorin A and deacetylgedunin (DCG) enriched plant extracts as novel inhibitors of Mpro, RBD–ACE2 and TMPRRS2 proteins DOI Creative Commons
Mariana J. Shayo,

Baraka Samwel,

Daniel M. Shadrack

и другие.

RSC Advances, Год журнала: 2024, Номер 14(29), С. 21203 - 21212

Опубликована: Янв. 1, 2024

The coronavirus disease 2019 (COVID-19) has spread worldwide with severe health, social, and economic repercussions. Although vaccines have significantly reduced the severity of symptoms deaths, alternative medications derived from natural products (NPs) are vital to further decrease fatalities, especially in regions low vaccine uptake. When paired latest computational developments, NPs, which been used cure illnesses infections for thousands years, constitute a renewed resource drug discovery. In present report, combination vitro methods reveals repositioning NPs identifies salvinorin A deacetylgedunin (DCG) as having potential anti-SARS-CoV-2 activities. Salvinorin was found both silico inhibit SARS-CoV-2 spike/host ACE2 protein interactions, consistent blocking viral cell entry, well live virus replication. Plant extracts Azadirachta indica Cedrela odorata, contain high levels DCG, inhibited replication by targeting main protease (Mpro) and/or entry interaction between spike RBD-ACE2 at concentrations lower than A. Our findings suggest that represent promising chemical starting points where optimization may result effective product-derived potent inhibitors supplement efforts.

Язык: Английский

Процитировано

1
Computer-aided design, synthesis, and biological evaluation of 4-chloro-N-(2-oxo-3-(2-pyridin-4-yl)hydrazineylidene)indolin-5yl)benzamide and 1-(4-bromobenzyl)-5-indoline-2,3-dione against SARS-CoV-2 spike/ACE2 DOI Creative Commons

Vanessa Asoh Shu,

Donatus Bekindaka Eni,

Mathieu Jules Mbenga Tjegbe

и другие.

The Microbe, Год журнала: 2024, Номер 4, С. 100143 - 100143

Опубликована: Авг. 15, 2024

The emergence of the severe acute respiratory syndrome 2 (SARS-CoV-2) as a global threat has driven urgent need for identification bioactive molecules capable controlling or completely eradicating this virus. Our group been investigating isatin hybrids that block binding human angiotensin-converting enzyme (ACE2) and viral spike protein. This work describes synthesis biological evaluation two derivatives (indol-2,3-dione) based on computational approach. Isatin, secondary metabolite tryptophan, used core structure is versatile favorable precursor privileged scaffold against complex. new compound scaffolds AVS-01 AVS-02 were designed by modifications at C-3 N-1 positions, respectively, according to various reagents available in our lab. Molecular docking compounds was explore their interactions with target protein shown article showed quite distinct glide scores (GScore = −3.657 −4.534 AVS-02, respectively). Several analogs synthesized tested quest find plausible further synthesis. While inhibition spike/ACE2 an IC50 value 8.8 µM, reference hopeaphenol inhibited interaction 0.3 µM. Compound rather no SARS-CoV-2 spike/host ACE2 > 32 An estimation free energy (ΔGbind), solvation (ΔGsolv) MM-GBSA calculations carried out re-evaluate affinity gain insights into observed activity non-activity. calculation ΔGbind −35.91 kcal/mol and-25.32 ΔGsolv 25.56 16.92 respectively. leads conclusion position indole-2,3-dione moiety favors blockage compared position. Analysis GScores, per-residue energies, energies van der Waals should favor towards

Язык: Английский

Процитировано

1