In Vitro Enzymatic and Computational Assessments of Pyrazole–Isatin and Pyrazole–Indole Conjugates as Anti-Diabetic, Anti-Arthritic, and Anti-Inflammatory Agents

Pharmaceutics, Год журнала: 2025, Номер 17(3), С. 293 - 293

Опубликована: Фев. 23, 2025

Background/Objectives: Recently, the prevalence of diseases such as diabetes, arthritis, and inflammatory diseases, along with their complications, has become a significant health problem. This is in addition to various biomedical applications pyrazole, isatin, indole derivatives. Accordingly, cooperation will continue between chemistry scientists, pharmaceutical human doctors produce hybrid compounds from pyrazole isatin or possessing biological activities anti-diabetic, anti-arthritic, anti-inflammatory agents. Methods: The two series pyrazole–isatin conjugates 12a–h pyrazole–indole 14a–d were prepared our previous works via direct reaction 5-amino-pyrazoles 10a–d N-alkyl 11a,b, 1H-indole-3-carbaldehyde (13), respectively, using previously reported procedure. potential agents assessed through estimated inhibition percentage (%) median inhibitory concentrations (IC50) methods described literature. Further, computational assessments toxic doses (the lethal dose, LD50), toxicity classes, drug-likeness model scores (DLMS), molecular lipophilicity (MLP) maps, polar surface area (PSA) topological (TPSA) values predicted available free websites. Results: vitro enzymatic assessment results showed that conjugate 14b possesses powerful against (i) α-amylase (% = 65.74 ± 0.23, IC50 4.21 0.03 µg/mL) α-glucosidase 55.49 2.76 0.01 µg/mL); (ii) protein denaturation enzyme 49.30 0.17) proteinase 46.55 an value 6.77 µg/mL; (iii) COX-1, COX-2, 5-LOX enzymes 5.44 0.03, 5.37 0.04, 7.52 which almost close indomethacin zileuton drugs. Also, lipophilic properties thus can cross cell membranes, effective for treatment; all possess TPSA more than 140 Å2 good intestinal absorption. Conclusions: synthesized works. these concluded studied results. In future, research team present vitro, vivo biological, hopefully obtain effectual anti-inflammatory.

Язык: Английский

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Development of novel triconjugates fusing melatonin/isatin/N-acylhydrazone targeting colorectal cancer: design, synthesis, biological, and in silico ADME/Tox profiling

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 23, 2025

Язык: Английский

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Synthesis of Dimeric Indoles from Friedel–Crafts Reaction of Indoles with Ketones Catalysed by a Bronsted Acid Ionic Liquid and Their Interactions with BSA and DNA

New Journal of Chemistry, Год журнала: 2024, Номер 48(34), С. 14904 - 14923

Опубликована: Янв. 1, 2024

The synthesis of 35 dimeric indole derivatives was carried out by using [BCMIM][Cl] ionic liquid as a catalyst. binding interaction between bovine serum albumin (BSA)/deoxyribonucleic acid (DNA) and synthesized compounds has been investigated.

Язык: Английский

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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

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

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Methyl 2-[(Z)-5-methyl-2-oxoindolin-3-ylidene]hydrazinecarbodithioate

IUCrData, Год журнала: 2024, Номер 9(10)

Опубликована: Окт. 8, 2024

The title di-thio-carbazate imine, C

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Design and Synthesis of Isatin‐1,2,3‐triazole Hybrids as Anticancer Agents

ChemistrySelect, Год журнала: 2024, Номер 9(47)

Опубликована: Дек. 1, 2024

Abstract Isatin, a chemically defined indole‐1 H ‐2,3‐dione, is widely considered desirable therapeutic fragment in the field of drug discovery. Similarly, 1,2,3‐triazole ring major pharmacophore system among nitrogen containing heterocycles. Molecular hybrids comprising isatin and acyl azides functions linked by triazole rings were synthesized tested for cytotoxic effects against sixty human cancer cell lines due to resistance with most currently utilized anticancer medicines. The 1,2,3‐triazole‐isatin (8a–8j) produced high yields exceptional purity via Huisgen's 1,3‐dipolar cycloaddition involving azide, 7a–7j , an Isatin‐based N ‐alkyne 3 presence water as principal solvent n ‐Bu‐OH DMF cosolvents. compounds 8c 8g 8h showed highly effective growth inhibition breast, leukemia, melanoma lines, mortality ranging from 6% 99% PGI = >70% majority instances. While 8a 8b weak moderate action all line few 8d 8f 8i, 8j shows low activity. A molecular docking study cyclin‐dependent kinase (CDK2) could provide insights into mechanistic basis antitumor

Язык: Английский

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Biological Activity Evaluation of Phenolic Isatin-3-Hydrazones Containing a Quaternary Ammonium Center of Various Structures

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(20), С. 11130 - 11130

Опубликована: Окт. 17, 2024

A series of new isatin-3-hydrazones bearing different ammonium fragments was synthesized by a simple and easy work-up reaction Girard's reagents analogs with 1-(3,5-di-

Язык: Английский

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Isatin Bis-Imidathiazole Hybrids Identified as FtsZ Inhibitors with On-Target Activity Against Staphylococcus aureus

Antibiotics, Год журнала: 2024, Номер 13(10), С. 992 - 992

Опубликована: Окт. 19, 2024

In the present study, a series of isatin bis-imidathiazole hybrids was designed and synthesized to develop new class heterocyclic compounds with improved antimicrobial activity against pathogens responsible for hospital- community-acquired infections. A remarkable inhibitory

Язык: Английский

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Novel isatin conjugates endowed with analgesic and anti-inflammatory properties: design, synthesis and biological evaluation

Future Medicinal Chemistry, Год журнала: 2024, Номер unknown, С. 1 - 15

Опубликована: Дек. 16, 2024

Aims This study aimed to develop novel molecular hybrid conjugates integrating isatin, rhodanine, and phthalimide pharmacophores create effective analgesic anti-inflammatory agents with improved safety profiles over existing treatments.

Язык: Английский

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