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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Green and efficient one-pot three-component synthesis of novel drug-like furo[2,3-d]pyrimidines as potential active site inhibitors and putative allosteric hotspots modulators of both SARS-CoV-2 MPro and PLPro

Bioorganic Chemistry, Год журнала: 2023, Номер 135, С. 106390 - 106390

Опубликована: Янв. 28, 2023

Язык: Английский

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Synthesis, characterization, molecular dynamic simulation, and biological assessment of cinnamates linked to imidazole/benzimidazole as a CYP51 inhibitor

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 41(21), С. 11518 - 11534

Опубликована: Янв. 24, 2023

A class of 2-(1H-imidazol-1-yl)-1-phenylethyl cinnamates 6a-6j and 2-(1H-benzo[d]imidazol-1-yl)-1-phenylethyl 7a-7j were synthesized, their synthesis was validated using various spectroscopic techniques like IR, NMR, Mass spectrometry. In addition, the compounds assessed for in-vitro antibacterial against gram-positive gram-negative strains antifungal six different fungal strains. Compounds 6 g, 7 b, 7f, g exhibited significant activity all bacterial ranging from MIC = 12.5-50 µg/mL, considerable MFC 125-200 µg/mL. molecular docking study indicated that 7j could be lodged in active pocket inhibit C. albicans Sterol 14α-demethylase (CYP51) protein via interactions, these studies validate results. Different parameters 100 ns MD simulation are investigated to evaluate dynamic stability protein-ligand complexes. According study, proposed effectively kept interaction structural integrity within 14-demethylase. promising lead searching novel drug-like molecules. Furthermore, silico ADME indicates possess physicochemical properties orally bioavailable.Communicated by Ramaswamy H. Sarma.

Язык: Английский

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Exploring the cytotoxic effect and CDK-9 inhibition potential of novel sulfaguanidine-based azopyrazolidine-3,5-diones and 3,5-diaminoazopyrazoles

Bioorganic Chemistry, Год журнала: 2023, Номер 133, С. 106397 - 106397

Опубликована: Фев. 1, 2023

Язык: Английский

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Design, synthesis, molecular docking, dynamics simulations and antiviral activities of quinoline derivatives

Journal of Molecular Structure, Год журнала: 2024, Номер 1319, С. 139531 - 139531

Опубликована: Авг. 2, 2024

Язык: Английский

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Design, synthesis, and mechanistic insight of novel imidazolones as potential EGFR inhibitors and apoptosis inducers

Bioorganic Chemistry, Год журнала: 2024, Номер 144, С. 107105 - 107105

Опубликована: Янв. 8, 2024

Язык: Английский

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Molecular modeling and DFT studies of diazenylphenyl derivatives as a potential HBV and HCV antiviral agents

Chemical Physics Impact, Год журнала: 2022, Номер 5, С. 100122 - 100122

Опубликована: Ноя. 7, 2022

• Some novel compounds Synthesized as antiviral drug for HBC and HCV NBO analysis used to explain charge transfer of the synthesized leading stability The titled molecules gave better binding affinity compared Tolbivudine Sofosbuvir which are standard drugs compound C, has highest second order perturbation energies but least reactive. need particularly hepatitis B (HBV) C (HCV) virus cannot be over emphasized hence, this work focuses on intermolecular interaction three diazenylphenyl compounds; 5-((E)-(4-((E)-(3-hydroxy-nitrosonaphthalen-1-yl)diazinyl)phenyl)diazinyl)-3,8a-dihydroquinolin-8-ol, (Z)-4-(E-(4-(E)-(2,4-dihydroxyphenyl)phenyl)diazinyl-2-(hydroxyamino)-4a,8a-dihyroapthalen-1(2H)-one, 4-((E)-(4-((E)-(2-hydroxy-3-nitrosophenyl)diazenyl)phenyl)diazenyl)-4a,8a-dihydronaphthalen-1(4H)-one depicted A, respectively. We have performed a comprehensive quantum computational study ascertain likeness molecules. Interestingly, Compound was found most stable A B. In Density state (DOS) studies, hydrogen observed peak in antibonding region whereas carbon values at bonding molecular orbitals. energies. dynamics simulation individual indicate that + 4MWF complex energy than other complexes RMSD targeted K7F, 6CWT, 5YAX proteins more conformationally when bound with Antiviral property investigated by docking selected viral proteins. studied were Telbivudine sofosbuvir drugs.

Язык: Английский

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Synthesis, docking, and biological investigations of new coumarin-piperazine hybrids as potential antibacterial and anticancer agents

Journal of Molecular Structure, Год журнала: 2022, Номер 1276, С. 134755 - 134755

Опубликована: Дек. 5, 2022

Язык: Английский

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The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro , and in silico mechanistic investigations

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 41(21), С. 12411 - 12425

Опубликована: Янв. 20, 2023

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to lack effective targeted medications, often resulting in recurrence metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival patients. Pyranopyrazole pyrazolone privileged development anticancer agents. Inspired by this proven scientific fact, we report here synthesis two new series suggested molecules incorporating both heterocycles together their characterization IR, 1H NMR, 13C NMR-DEPT, X-ray diffraction methods. An attempt get pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. unexpected result confirmed crystallographic analysis. All newly synthesized compounds were assessed anti-proliferative activity against different human cells, obtained results compared reference drug Staurosporine. The target revealed variable cytotoxicity IC50 at a low micromolar range superior selectivity indices. Target enzyme EGFR-TK CDK-9 assays showed 22 23 effectively inhibited biological targets values 0.143 0.121 µM, respectively. Molecular docking experiments molecular dynamics simulation also further rationalize vitro results.Communicated Ramaswamy H. Sarma.

Язык: Английский

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A novel class of phenylpyrazolone-sulphonamides rigid synthetic anticancer molecules selectively inhibit the isoform IX of carbonic anhydrases guided by molecular docking and orbital analyses

Journal of Biomolecular Structure and Dynamics, Год журнала: 2023, Номер 41(24), С. 15243 - 15261

Опубликована: Март 13, 2023

All the previously reported phenylpyrazoles as carbonic anhydrase inhibitors (CAIs) were found to have small sizes and high levels of flexibility, hence showed low selectivity profiles toward a particular isoform CA. Herein, we report development more rigid ring system bearing sulfonamide hydrophilic head lipophilic tail develop novel molecules that are suggested better special CA isoform. Accordingly, three sets pyrano[2,3-c]pyrazoles attached with aryl hydrophobic synthesized enhance specific human anhydrases (hCAs). The impact both attachments on potency has been extensively discussed in terms vitro cytotoxicity evaluation under hypoxic conditions, structure-activity relationship enzyme assay. new candidates displayed good cytotoxic activities against breast colorectal carcinomas. Results assay demonstrated preferential compounds 22, 24 27 inhibit IX hCAs selectively. Wound-healing also performed revealed potential decrease wound closure percentage MCF-7 cells. Molecular docking molecular orbital analysis finally conducted. indicate binding interactions several crucial amino acids hCA IX.Communicated by Ramaswamy H. Sarma.

Язык: Английский

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