Phenylpyrazolone-1,2,3-triazole Hybrids as Potent Antiviral Agents with Promising SARS-CoV-2 Main Protease Inhibition Potential

Pharmaceuticals, Год журнала: 2023, Номер 16(3), С. 463 - 463

Опубликована: Март 20, 2023

COVID-19 infection is now considered one of the leading causes human death. As an attempt towards discovery novel medications for pandemic, nineteen compounds containing 1,2,3-triazole side chains linked to phenylpyrazolone scaffold and terminal lipophilic aryl parts with prominent substituent functionalities were designed synthesized via a click reaction based on our previous work. The assessed using in vitro effect growth SARS-CoV-2 virus-infested Vero cells different compound concentrations: 1 10 μM. data revealed that most these derivatives showed potent cellular anti-COVID-19 activity inhibited viral replication by more than 50% no or weak cytotoxic harboring cells. In addition, assay employing SARS-CoV-2-Main protease inhibition was done test inhibitors' ability block common primary virus as mode action. obtained results show non-linker analog 6h two amide-based linkers 6i 6q active IC50 values 5.08, 3.16, 7.55 μM, respectively, against comparison selective antiviral agent GC-376. Molecular modeling studies placement within binding pocket which reveal conserved residues hydrogen bonding non-hydrogen interactions fragments: triazole scaffold, part, linker. Moreover, stability their target also studied analyzed molecular dynamic simulations. physicochemical toxicity profiles predicted, behave low organ toxicity. All research point potential usage new chemotype promising leads be explored vivo might open door rational drug development Main medicines.

Язык: Английский

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Design and synthesis of new spirooxindole candidates and their selenium nanoparticles as potential dual Topo I/II inhibitors, DNA intercalators, and apoptotic inducers

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2023, Номер 38(1)

Опубликована: Авг. 18, 2023

A new wave of dual Topo I/II inhibitors was designed and synthesised via the hybridisation spirooxindoles pyrimidines. In situ selenium nanoparticles (SeNPs) for some derivatives were synthesised. The targets SeNP examined their cytotoxicity towards five cancer cell lines. inhibitory potencies best members against I II also assayed besides DNA intercalation abilities. Compound 7d NPs exhibited inhibition enzymes with IC50 0.042 1.172 μM, respectively. ability compound to arrest cycle induce apoptosis investigated. It arrested in A549 at S phase prompted by 41.02% vs. 23.81% control. silico studies then performed study possible binding interactions between target proteins.

Язык: Английский

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New pyranopyrazole based derivatives: Design, synthesis, and biological evaluation as potential topoisomerase II inhibitors, apoptotic inducers, and antiproliferative agents

Bioorganic Chemistry, Год журнала: 2024, Номер 144, С. 107158 - 107158

Опубликована: Янв. 29, 2024

Язык: Английский

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Unraveling the interaction of pyranocoumarins with P-glycoprotein: Implications for overcoming multidrug resistance in cancer therapy

Bioorganic Chemistry, Год журнала: 2025, Номер 158, С. 108314 - 108314

Опубликована: Март 4, 2025

Язык: Английский

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A decade of research effort in synthesis, biological activity assessments, and mechanistic investigations of sulfamethazine‐incorporating molecules

Archiv der Pharmazie, Год журнала: 2025, Номер 358(3)

Опубликована: Март 1, 2025

Abstract Because of its importance in medicinal chemistry, scientific researchers have been interested incorporating sulfamethazine developing biologically active candidates. To achieve this, several synthetic approaches adopted. The adopted included condensation with electrophilic reactants, coupling nucleophilic aromatics and methylene compounds, Knoevenagel condensation, Doebner Miller reaction, microwave‐assisted click cycloaddition, green reaction routes, multicomponent reaction. Linking this molecular scaffold to a variety heterocycles the last 10 years furnished set potential anti‐inflammatory, antiviral, anticancer, antiparkinsonian, neuroprotective, antidiabetic candidates targeting H5N1 NA, epidermal growth factor receptor, acetylcholinesterase (AChE), butylcholinesterase (BChE), human carbonic anhydrase ( h CA), α‐amylase, α‐glucosidase. This review reports all approaches, biological activities studied, structure‐activity relationship analyses, mechanistic investigations reported organic sulfamethazine‐incorporating molecules throughout 2015–2024, based on information retrieved from three search engines: Scopus, PubMed, Google Scholar.

Язык: Английский

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Novel Benzimidazole‐1,2,3‐Triazole Hybrids: Synthesis, Dual Antimicrobial, Anticancer Activity, Mechanistic Insights, and Computational Studies

ChemistrySelect, Год журнала: 2025, Номер 10(15)

Опубликована: Апрель 1, 2025

Abstract This study reports the synthesis and biological evaluation of two series novel hybrid heterocyclic scaffolds tethering 1,2,3‐triazole benzimidazole moieties using click chemistry approach. Aromatic azides were synthesized from aniline derivatives followed by preparation S‐propargylated intermediates. These intermediates then reacted with through 1,3‐dipolar cycloaddition to yield benzimidazole‐1,2,3‐triazole hybrids. The compounds fully characterized NMR spectroscopy. Biological testing revealed significant antibacterial, antifungal, cytotoxic activities. Notably, acetamide‐linked 1,2,3‐triazole‐benzimidazole hybrids exhibited potent activity against Gram‐negative bacteria fungal strains MIC values 0.156–0.312 mg/mL several demonstrating selectivity cancer cell lines, particularly HepG‐2 A‐549 IC 50 7–30 µg/mL. EGFR‐TK enzyme inhibition assays further highlighted potential these as anticancer agents. Docking simulation was done for most active 5d 9f promising triazole hits different linker structures interaction analogs both valuable targets contributing growth such as; EGFRWT EGFRT790 in disease; fragments contributions are able stabilize molecular interactions. bioactivity positions them candidates optimization development broad‐spectrum antimicrobial

Язык: Английский

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Novel benzochromenes: design, synthesis, cytotoxicity, molecular docking and mechanistic investigations

Future Medicinal Chemistry, Год журнала: 2024, Номер 16(2), С. 105 - 123

Опубликована: Янв. 1, 2024

Aim: A novel series of fused benzochromenes with expected cytotoxicity and HIF-1α inhibition was identified. Materials & methods: bioisosterism-aided approach applied to design new assess their against three cancer cell lines. The probable mechanistic effect the in silico docking pharmacokinetic profiles most effective derivatives were evaluated. Results: Compounds 3, 4, 5, 8 11 showed potent antiproliferative activity excellent selectivity. Compound significant an IC50 value 3.372 μM. It also enhanced apoptosis arrested HepG2 cycle at both G0/G1 S stages. Conclusion: identified as a potential anticancer candidate.

Язык: Английский

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Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

Archiv der Pharmazie, Год журнала: 2024, Номер 357(7)

Опубликована: Апрель 29, 2024

Abstract Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring chemistry various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) one biologically active targets for curing diseases. The widespread distribution these enzymes and high degree homology shared isoforms offer substantial challenges to discovering potential Medicinal synthetic organic have been continuously involved in developing CA inhibitors. This review explored inhibitors using last 11 years published research work. It provides a pathway young researchers further explore variety well natural

Язык: Английский

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In vivo evaluation of novel synthetic pyrazolones as CDK9 inhibitors with enhanced pharmacokinetic properties

Future Medicinal Chemistry, Год журнала: 2024, Номер unknown, С. 1 - 19

Опубликована: Ноя. 12, 2024

The structural optimization of our recently reported CDK9 inhibitor to furnish novel aminopyrazolones and methylpyrazolones with improved pharmacokinetics.

Язык: Английский

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Molecular overlay-guided design of new CDK2 inhibitor thiazepinopurines: Synthesis, anticancer, and mechanistic investigations

Bioorganic Chemistry, Год журнала: 2023, Номер 140, С. 106789 - 106789

Опубликована: Авг. 17, 2023

Язык: Английский

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