An evaluation of spirooxindoles as blocking agents of SARS-CoV-2 spike/ACE2 fusion and M pro inhibitory agents: Synthesis, biological evaluation and computational analysis DOI Creative Commons

Albert Enama Ehinak,

Maloba M. M. Lobe, Conrad V. Simoben

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities, including antiviral activity. They are, therefore, recognized as privileged scaffolds in drug discovery. Here, we describe the synthesis spirofused tetrahydroisoquinoline–oxindole hybrids (spirooxindoles) their evaluation potential blocking agents both SARS-CoV-2 spike/ACE fusion inhibitors main protease (Mpro). The most active synthesized compound showed 50% inhibitory concentration (IC50) 3.6 µM against fusion. None tested compounds was shown to be Mpro. possesses bulky naphthyl group, which addresses voluminous hydrophobic regions ACE2 binding site interacts with residues target; this finding agrees previous studies revealing that block spike/ACE2 fusion, e.g., natural product hopeaphenol. Therefore, spirooxindoles may provide useful leads search for agents.

Language: Английский

An evaluation of spirooxindoles as blocking agents of SARS-CoV-2 spike/ACE2 interaction: synthesis, biological evaluation and computational analysis DOI Creative Commons

Albert Enama Ehinak,

Maloba M. M. Lobe, Donatus Bekindaka Eni

et al.

Medicinal Chemistry Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Language: Английский

Citations

0
Advances in the Design, Discovery, and optimization of aurora kinase inhibitors as anticancer agents DOI
Anita Verma,

Pradhuman Bharatiya,

Aashish Jaitak

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 17, 2025

Introduction Aurora kinases (AKs) play key roles during carcinogenesis and show a close relationship with many cellular effects including mitotic entry, spindle assembly chromosomal alignment biorientation. Indeed, elevated levels of AKs have been reported in several different tumor types, leading research scientists to investigate ways that we can target for the purpose developing new anticancer therapeutics.

Language: Английский

Citations

0
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

et al.

The Microbe, Journal Year: 2024, Volume and Issue: 4, P. 100143 - 100143

Published: Aug. 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

Language: Английский

Citations

1
Recent advancements in mechanistic Research, therapeutic Potential, and Structure-Activity relationships of Aurora kinase inhibitors in cancer therapies DOI
Ghanshyam Teli, Lalmohan Maji, Rohit Pal

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 154, P. 107976 - 107976

Published: Nov. 16, 2024

Language: Английский

Citations

1
An evaluation of spirooxindoles as blocking agents of SARS-CoV-2 spike/ACE2 fusion and M pro inhibitory agents: Synthesis, biological evaluation and computational analysis DOI Creative Commons

Albert Enama Ehinak,

Maloba M. M. Lobe, Conrad V. Simoben

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: June 21, 2024

Abstract Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities, including antiviral activity. They are, therefore, recognized as privileged scaffolds in drug discovery. Here, we describe the synthesis spirofused tetrahydroisoquinoline–oxindole hybrids (spirooxindoles) their evaluation potential blocking agents both SARS-CoV-2 spike/ACE fusion inhibitors main protease (Mpro). The most active synthesized compound showed 50% inhibitory concentration (IC50) 3.6 µM against fusion. None tested compounds was shown to be Mpro. possesses bulky naphthyl group, which addresses voluminous hydrophobic regions ACE2 binding site interacts with residues target; this finding agrees previous studies revealing that block spike/ACE2 fusion, e.g., natural product hopeaphenol. Therefore, spirooxindoles may provide useful leads search for agents.

Language: Английский

Citations

0