Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(9), P. 1828 - 1881

Published: April 22, 2024

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a–h), hydrazine monohydrate (NH2NH2•H2O) for regioselective preparation some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a–h). After synthesis characterization mentioned cinnolines (3a–h), in silico multi-targeting inhibitory properties these heterocyclic scaffolds investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, hDHODH, which confirmed their functions roles neurodegenerative (NDs), based on molecular docking studies, obtained results were compared with wide range approved drugs well-known (with IC50, EC50, etc.) compounds. addition, ADMET prediction analysis was performed examine prospective drug synthesized compounds The from studies ADMET-related data demonstrated that series heteroaryl)-5,6-dihydrobenzo[h]cinnolines especially hit ones, can really be turned into potent core new treatment and/or due having reactionable locations, they able further organic reactions (such as cross-coupling reactions), expansion (for example, using other types monohydrates) makes avenue designing novel efficient purpose.

Language: Английский

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Computer-aided drug design of novel nirmatrelvir analogs inhibiting main protease of Coronavirus SARS-CoV-2

Journal of Applied Pharmaceutical Science, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

A computer-aided drug design of new derivatives nirmatrelvir, an orally active inhibitor the main-protease (Mpro) severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), was performed to identify its analogues with a higher antiviral potency. The following workflow used: first, evolutionary library composed 1,866 generated starting from parent nirmatrelvir scaffold and going through small mutation, fitness scoring, ranking, selection. Second, preprocessed filtered against 3-D pharmacophore model built X-ray structure in co-crystalized complex Mpro enzyme, allowing us reduce chemical space 32 analogues. Third, structure-based molecular docking two different enzyme structures further ranked these candidates, so that up eight better-binding analogs were identified. selected hit-analogues target enzymes SARS-CoV-2 binding affinity than nirmatrelvir. main structural modifications increase overall inhibitory are identified at azabicyclo[3.1.0] hexane 2-oxopyrrolidine fragments. characteristic feature centre is similar location trifluoroacetylamino fragment, which observed for most hit-analogues. suggested rational noncovalent inhibitors based on approved drugs promising, extremely low-cost, time-efficient approach development potential pharmaceutical ingredients treatment Disease 2019.

Language: Английский

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Furo, Pyrano, and Pyrido[2,3‐d]Pyrimidines: A Comprehensive Review of Synthesis and Medicinal Applications

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(10)

Published: March 7, 2024

Abstract Due to their extensive applications in pharmaceuticals and natural substances, organic synthesis heterocyclic compounds have been at the forefront of research for many years. Pyrimidine is one that various derivatives with promising biological pharmacological properties. This review article covers effects pyrimidine derivatives, such as pyrano[2,3‐ d ]pyrimidines, pyrido[2,3‐ furo[2,3‐ ]pyrimidines. The discussed this a wide range activities. Recent advances green chemistry led development eco‐friendly synthetic methods producing these bioactive heterocycles. aims present provide new opportunities chemists develop potent nitrogen‐ oxygen‐containing heterocycles future applications. highlights examples successful syntheses fields antibacterial, antifungal, anticancer, enzyme inhibition, antiviral research.

Language: Английский

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Highly efficient synthesis of isoxazolones and pyrazolones using g-C3N4·OH nanocomposite with their in silico molecular docking, pharmacokinetics and simulation studies

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Aug. 18, 2024

An environmentally friendly, versatile multicomponent reaction for synthesizing isoxazol-5-one and pyrazol-3-one derivatives has been developed, utilizing a freshly prepared g-C

Language: Английский

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Immobilized nickel boride nanoparticles on magnetic functionalized multi-walled carbon nanotubes: a new nanocomposite for the efficient one-pot synthesis of 1,4-benzodiazepines

Nanoscale Advances, Journal Year: 2023, Volume and Issue: 5(17), P. 4499 - 4520

Published: Jan. 1, 2023

In this study, a new magnetic nanocomposite consisting of Ni2B nanoparticles anchored on functionalized multi-walled carbon nanotubes (Fe3O4/f-MWCNT/Ni2B) was synthesized and characterized using various techniques such as FT-IR, XRD, FESEM, SEM-based EDX, elemental mapping, HRTEM, DLS, SAED, XPS, BET, TGA, VSM. The as-prepared successfully employed for the preparation bioactive 1,4-benzodiazepines from three-component reaction o-phenylenediamine (1), dimedone (2), different aldehydes (3), in polyethylene glycol 400 (PEG-400) solvent at 60 °C. obtained results demonstrated that current one-pot protocol offers many advantages, good-to-excellent yields within acceptable times, favorable TONs TOFs, eco-friendliness procedure, easy nanocomposite, mild conditions, broad range products, excellent catalytic activity, green solvent, reusability nanocomposite.

Language: Английский

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Antitumor Effects of Tryptanthrin on Colorectal Cancer by Regulating the Mitogen-Activated Protein Kinase Signaling Pathway and Targeting Topo I and IDO1

ACS Omega, Journal Year: 2025, Volume and Issue: 10(3), P. 3206 - 3221

Published: Jan. 10, 2025

Tryptanthrin (TRYP) is an indole quinazoline alkaloid with a range of pharmaceutical activities, but the specific mechanism TRYP against colorectal cancer (CRC) remains obscure. The purpose this study was to evaluate antitumor effects on CRC models both in vitro and vivo further analyze its concrete mechanisms. results experiment show that effectively inhibited proliferation migration SW620 cells, arrested cell cycle at S phase, induced apoptosis. Deeply, dramatically increased expression Bax cleaved caspase 3 while decreasing Bcl-2. transcriptome sequencing implied inhibitory were closely related mitogen-activated protein kinase (MAPK) signaling pathway, western blotting verified could decrease p-Erk increase p-p38 p-Jnk. Besides, our identified topoisomerase I (Topo I) amine 2,3-dioxygenase 1 (IDO1) targets TRYP. In vivo, showed different doses significantly tumor growth mice, degrees necrosis tissues, decreased level Ki67 protein, apoptotic signal tissues. findings demonstrated CRC, mechanisms tightly connected inhibiting activity Topo IDO1 regulating MAPK pathway. Especially, it first directly inhibit arrest phase. Therefore, work established scientific basis for development

Language: Английский

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Green synthesis of benzimidazoles via the palladium catalyzed one-pot reductive coupling of nitroarylamines with nitriles

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 141747 - 141747

Published: Feb. 1, 2025

Language: Английский

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Green procedures for synthesizing potential hNMDA receptor allosteric modulators through reduction and one-pot reductive acetylation of nitro(hetero)arenes using a superparamagnetic Fe₃O₄@APTMS@Cp₂ZrCl_{x (x = 0, 1, 2)} nanocatalyst

Nanoscale Advances, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

In this research, we have developed diverse strategies for synthesizing potential h NMDA receptor allosteric modulators through reduction and one-pot reductive acetylation of nitro(hetero)arenes using a mesoporous zirconocene-containing nanocatalyst.

Language: Английский

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Comprehensive Phytochemical, Antioxidant, and Antibacterial Analysis of Vitex agnus-castus L. Essential Oil (VACEO): Insights from ADMET and Molecular Docking Studies

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 462 - 462

Published: March 25, 2025

Background/Objectives: The phytochemical composition, antioxidant, and antibacterial properties of Vitex agnus-castus L. essential oil (VACEO), extracted from fruit harvested in the Middle Atlas region Morocco, were investigated. Methods/Results: A full chemical analysis VACEO was performed to identify principal components using GC–MS, demonstrating that caryophyllene (13.87%), 1-(4-Isopropylphenyl)-2-methylpropyl acetate (12.20%), τ-Cadinol (5.41%) most important constituents this oil. In addition, antioxidant activity evaluated DPPH, FRAP, TAC, beta-carotene bleach tests; demonstrated an IC50 0.93 ± 0.03 mg/mL (DPPH), EC50 0.146 0.004 (FRAP), a total capacity 0.794 0.02 mg BHT equivalent/g EO, with relative at 72.69 0.3%. Antibacterial assays revealed inhibition diameters ranging 13.25 1.00 mm 21.11 0.25 mm, minimum inhibitory concentrations (MICs) 0.02–0.04 against Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa. Moreover, ADMET suggested potential for drug development, specific insights into pharmacokinetics, safety, molecular docking, clarifying its interactions key bacterial proteins. Conclusions: These results confirm promising therapeutic pharmaceutical through bioactive compounds.

Language: Английский

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Green and Tandem Synthesis of Heterocyclic α,α’‐Dibromocycloamides and Their Target Predictions and ADMET Analysis

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(16)

Published: April 1, 2025

Abstract Oxy‐bromination of cyclic amines to corresponding α,α’‐dibromocycloamide(s) using bromide‐bromate couple in aqueous acetic acid and at 60 °C (oil bath) is presented the current work. A various types were successfully oxybrominated during this Separation desired product by filtration therefore avoiding need column chromatography, use as safe stable source oxy‐bromination agent, mild reaction conditions so on are merits present research method. In silico ADMET target prediction studies indicated that novel α,α’‐dibromocycloamides possess satisfactory pharmacokinetic pharmacodynamic profiles. The identified therapeutic targets provided a foundation for developing optimized molecules targeting therapeutically significant classes. HOMO‐LUMO energy calculations DFT method showed Mole 3 4 exhibited low gap demonstrated high reactivity. However, 5, 6, 7 9 found with energy, thereby producing less reactivity or stability. reactive could be potential lead which can interact efficiently drug targets. further experimental (in vitro/in vivo) necessary gain deeper insights into pharmacological activities these compounds.

Language: Английский

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