Synthesis, molecular modeling Insights, and anticancer assessment of novel polyfunctionalized Pyridine congeners

Abouelenein, Mohamed G.; El-Rashedy, Ahmed A.; Awad, Hanem M.; El Farargy, Ahmed F.; Nassar, Ibrahim F.; Nassrallah, Amr

doi:10.1016/j.bioorg.2023.106910

Cited by 5 publications

(3 citation statements)

References 95 publications

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“…All the data files were displayed using GaussianView6 [ 55 ]. To optimize the organic chemical structure of compound 18 , the density function theory (DFT) at 6-31G++(d,p) basis set/B3LYP method was applied, and Avogadro software 1.2.0 was used to generate and optimize the original chemical structure [ 67 , 68 ].…”

Section: Methodsmentioning

confidence: 99%

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies

Allayeh,

El-boghdady,

Said

et al. 2024

Pharmaceuticals

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The SARS-CoV-2 pandemic at the end of 2019 had major worldwide health and economic consequences. Until effective vaccination approaches were created, the healthcare sectors endured a shortage of operative treatments that might prevent the infection’s spread. As a result, academia and the pharmaceutical industry prioritized the development of SARS-CoV2 antiviral medication. Pyranopyrazoles have been shown to play a prominent function in pharmaceutical chemistry and drug sighting because of their significant bioactive properties. We provide herein a novel sequence of pyranopyrazoles and their annulated systems whose antiviral efficacy and cytotoxicity were explored versus human coronavirus 229E (HCoV-229E) Vero-E6 cell lines as a model for the Coronaviridae family. Fifteen synthetic congeners pointed out miscellaneous antiviral efficacies against HCoV-229E with variable inhibition degrees. Compound 18 showed a high selectivity index (SI = 12.6) that established spectacular inhibitory capacity against human coronavirus 229E. Compounds 6, 7, and 14 exposed moderate efficacies. Compounds 6, 7, 14, and 18 exhibited substantial antiviral action through the replication phase with reduction percentages extending from 53.6%, 60.7%, and 55% to 82.2%, correspondingly. Likewise, when assessed to the positive control tipranavir (88.6%), the inhibitory efficiency of compounds 6, 7, 14, and 18 versus the SARS-CoV2 Mpro provided high percentages of 80.4%, 73.1%, 81.4% and up to 84.5%, respectively. In silico studies were performed to investigate further the biological activity and the target compounds’ physical and chemical features, including molecular dynamic (MD) simulations, protein–ligand docking, ADME studies, and density functional theory (DFT) calculations. These inquiries demonstrated that this series of metabolically stable pyranopyrazoles and their annulated systems are effective human coronavirus inhibitors that inhibit the viral Mpro protein and may have emerged as a novel COVID-19 curative option.

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Section: Methodsmentioning

confidence: 99%

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies

Allayeh,

El-boghdady,

Said

et al. 2024

Pharmaceuticals

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“…Today's huge spread of antibiotics in the medical field is attributed to extremely resilient microbes; hence, wide‐ranging efforts are still desirable for emerging effective antimicrobial agents. Relying on the Clinical and Laboratory Standards Institute (CLSI) references, the broth microdilution assay was accomplished, and antimicrobial activities were acknowledged as minimum inhibitory concentration (MIC) values occupying nystatin, ciprofloxacin, and griseofulvin as reference antibiotics [55] …”

Section: Methodsmentioning

confidence: 99%

“…Relying on the Clinical and Laboratory Standards Institute (CLSI) references, the broth microdilution assay was accomplished, and antimicrobial activities were acknowledged as minimum inhibitory concentration (MIC) values occupying nystatin, ciprofloxacin, and griseofulvin as reference antibiotics. [55] The test was executed in sterile 96-well microplates. Before the antimicrobial activity screening, aiming to attain 1024 μg/mL concentration, 10 mg of every compound was dispelled in dimethyl sulphoxide (DMSO).…”

Section: Antimicrobial Assessmentmentioning

confidence: 99%

Facile and Novel Synthetic Approach, Molecular Docking, Molecular Dynamics, and Drug‐Likeness Evaluation of 9‐Substituted Acridine Derivatives as Dual Anticancer and Antimicrobial Agents

Abouelenein,

Mohamed,

Elsenety

et al. 2024

Chemistry & Biodiversity

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In the present study, numerous acridine congeners A1‐A20 were synthesized via aromatic nucleophilic substitution (SNAr) reaction of 9‐chloroacridine with carbonyl hydrazides, amines, or phenolic derivatives depending upon facile, novel, and eco‐friendly approaches (Microwave and ultrasonication assisted synthesis). The newly compounds’ structures were explicated utilizing spectroscopic methods. The title products were assessed for their antimicrobial, antioxidant, and antiproliferative efficacies utilizing numerous assays. Auspiciously, the investigated compounds mainstream revealed auspicious antibacterial and anticancer efficacies. Thereafter, the investigated compounds’ expected mode of action was debated via employing an array of insilico studies. Compounds A2 and A3 were the most promising antimicrobial agent, while compounds A2, A5, and A7 revealed the most cytotoxic efficiencies. Accordingly, RMSD, RMSF, Rg, and SASA analyzes of compounds A2 and A3 were performed, and MMPBSA was calculated. Lastly, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) analyses of the novel acridine derivatives were investigated. The tested compounds’ existing screening results afford an inspiring basis leading to developing new compelling antimicrobial and anti‐cancer agents based on the acridine scaffold.

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Expanding the potential of pyridine scaffold for targeted therapy of cancer: Biological activity, Molecular insights, and Structure-activity relationship

Aishwarya,

Matada,

Pal

et al. 2024

Journal of Molecular Structure

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Synthesis, molecular modeling Insights, and anticancer assessment of novel polyfunctionalized Pyridine congeners

Cited by 5 publications

References 95 publications

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies

Discovery of Pyrano[2,3-c]pyrazole Derivatives as Novel Potential Human Coronavirus Inhibitors: Design, Synthesis, In Silico, In Vitro, and ADME Studies

Facile and Novel Synthetic Approach, Molecular Docking, Molecular Dynamics, and Drug‐Likeness Evaluation of 9‐Substituted Acridine Derivatives as Dual Anticancer and Antimicrobial Agents

Expanding the potential of pyridine scaffold for targeted therapy of cancer: Biological activity, Molecular insights, and Structure-activity relationship

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