Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors

Hekal, Hend A.; Hammad, Omar M.; El-Brollosy, Nasser R.; Salem, Maha M.; Allayeh, Abdou K.

doi:10.1016/j.bioorg.2024.107353

Cited by 4 publications

(1 citation statement)

References 41 publications

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“…Molecules containing phosphonate groups have demonstrated diverse bioactivities and have been successfully employed in medicinal and agrochemical applications. , In 2018, Chi and co-workers developed an enantioselective [4 + 2] cycloaddition reaction between α,β-unsaturated aldehydes 30 and α-ketophosphonates 31 . This reaction yielded a variety of 2-pyranylphosphonate products 32 bearing multiple functional groups with moderate yields and excellent er values.…”

Section: Nhc-catalyzed Synthesis Of Chiral Pesticide Active Moleculesmentioning

confidence: 99%

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

Yang,

Jiang,

Jin

et al. 2024

J. Agric. Food Chem.

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The different configurations of chiral pesticides generally have significant influence on their biological activities. Chiral agrochemicals with high optical purities have become a prominent topic in the research field of new pesticides due to their advantages including lower toxicity, higher efficiency, and reduced residue levels. However, most commercially available pesticides that possess chiral elements are still used in their racemic forms. To date, asymmetric catalysis has emerged as a versatile tool for the enantioselective synthesis of various chiral agrochemicals and novel chiral pesticide active molecules. This perspective provides a comprehensive overview of the applications of diverse asymmetric catalytic approaches in the facile preparation of numerous novel pesticide active molecules, and our own outlook on the future development of this highly active research direction is also presented at the end of this review.

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Section: Nhc-catalyzed Synthesis Of Chiral Pesticide Active Moleculesmentioning

confidence: 99%

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

Yang,

Jiang,

Jin

et al. 2024

J. Agric. Food Chem.

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Discovering the inhibition of YAP/TEAD Hippo signaling pathway via new pyrazolone derivatives: synthesis, molecular docking and biological investigations

Noser,

Salem,

Baren

et al. 2024

Sci Rep

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Inhibition of DRP-1 mitochondrial mitophagy and fission by novel α-aminophosphonates bearing pyridine: synthesis, biological evaluations, and computer-aided design

Hekal,

Salem,

El Salam

2024

BMC Chemistry

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Heterocyclic compounds play a crucial role in the drug discovery process and development due to their significant presence and importance. Here, we report a comprehensive analysis of α-aminophosphonates containing pyridine (3a–g), prepared according to a clear-cut, uncomplicated procedure. The phosphonates are thoroughly characterized using various methods, such as elemental analysis, mass spectrometry, proton and carbon NMR, and FT-IR. The molecular docking interactions between the phosphonate and DRP-1 target protein observed that compound 3d had the top-ranked binding energy towards DRP-1 with a value equal to − 9.54 kcal/mol and this theoretically proves its inhibitory efficacy against DRP-1 arbitrated mitochondrial fission. Besides, the anticancer characteristics of compound 3d showed the best IC50 against HepG-2, MCF-7, and Caco-2 which confirmed our results towards suppressing DRP-1 protein (in-silico), and it elucidated no cytotoxic effects against human normal cell line (WI-38). Further, its pharmacokinetics were observed theoretically using ADMET. Moreover,compound 3d investigated the most potent antimicrobial ability against two pathological fungal strains, A. flavus and C. albicans, and four bacterial strains, E. coli, B. subtillis, S. aureus, and P. aregeunosa. Additionally, compound 3d clarified a powerful antioxidant scavenging activity against DPPH and ABTS free radicals (in-vitro). Furthermore, Density functional theory (DFT) was used to study the molecular structures of the synthesized compounds 3a–g, utilizing 6–311++G(d,p) as the basis set and to learn more about the molecules’ reactive sites, the energies of the molecular electrostatic potential (MEP), the lowest unoccupied molecular orbital (LUMO), and the highest occupied molecular orbital (HOMO) were observed. Theoretically, FT-IR and Nuclear magnetic resonance (NMR) measurements are calculated for every compound under investigation to show how theory and experiment relate. It was found that there was an excellent agreement between the theoretical and experimental data. Conclusively, all novel synthesized phosphonates could be used as pharmaceutical agents against pathogenic microbial strains and as anticancer candidates by inhibiting DRP-1-mediated mitochondrial mitophagy.

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Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors

Cited by 4 publications

References 41 publications

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

Discovering the inhibition of YAP/TEAD Hippo signaling pathway via new pyrazolone derivatives: synthesis, molecular docking and biological investigations

Inhibition of DRP-1 mitochondrial mitophagy and fission by novel α-aminophosphonates bearing pyridine: synthesis, biological evaluations, and computer-aided design

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