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

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 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.

Язык: 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

и другие.

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 23, 2025

Язык: Английский

Процитировано

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

Pradhuman Bharatiya,

Aashish Jaitak

и другие.

Expert Opinion on Drug Discovery, Год журнала: 2025, Номер unknown

Опубликована: Март 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.

Язык: Английский

Процитировано

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

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
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

и другие.

Bioorganic Chemistry, Год журнала: 2024, Номер 154, С. 107976 - 107976

Опубликована: Ноя. 16, 2024

Язык: Английский

Процитировано

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

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 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.

Язык: Английский

Процитировано

0