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Molecular Modelling Simulations And Inhibitory Effects Of Naturally Derived Flavonoids Targeting Platelet-activating Factor Receptor (pafr)

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dc.contributor.authorNoraziah Nordinen_US
dc.contributor.authorJuriyati Jalilen_US
dc.contributor.authorMohd Faiz Abd Ghanien_US
dc.contributor.authorAdib Afandi Abdullahen_US
dc.contributor.authorRozana Othmanen_US
dc.date.accessioned2024-05-27T15:07:03Z
dc.date.available2024-05-27T15:07:03Z
dc.date.issued2021
dc.date.submitted2022-1-27
dc.descriptionLetters in Drug Design & Discovery 2022; 19(1)en_US
dc.description.abstractBackground: Platelet-activating factor (PAF) is an agonist mediator in the inflammatory process, which interacts with PAF receptor (PAFR) that eventually causes cancers, respiratory and neurodegenerative diseases. This interaction activates the mitogen-activated protein kinase (MAPK) pathway, leading to a pro-inflammatory cascade. The pathophysiological conditions due to activation of inflammatory cascade could be inhibited by PAF antagonists. Objectives: In this study, selected naturally derived flavonoids (flavone, biochanin A, and myricetin) with different functional groups were subjected to molecular modelling and experimental studies to investigate their potential as PAF antagonists. Methods: Interactions of flavonoids and PAF were assessed via Autodock Vina for molecular docking and the AMBER program for molecular dynamic simulations. The experimentally antagonistic effects of the flavonoids were also conducted via PAF inhibitory assay to determine the IC50 values. Results: The findings of docking and dynamic simulations have revealed that all selected flavonoids interact with PAFR in the binding site with considerably good binding affinity up to - 9.8 kcal mol-1 as compared to cedrol (- 8.1 kcal mol-1) as a standard natural PAFR antagonist. The PAFR-flavonoid complexes exhibited four conserved active site residues, which included W73, F97, F174, and L279. The stability of all complexes was attained in a 30 ns simulation. The findings of in silico analyses were then compared to the experimental study on PAF inhibitory assay. Inhibitory effects of flavonoids against PAFR showed moderate activities, ranging from 27.8 – 30.8 μgM-1. Conclusion: All studied flavonoids could act as promising PAF antagonists with some enhancement in their structures to exhibit potent antagonistic activity. However, these naturally derived flavonoids demand further investigation at cellular and animal models to develop new PAF antagonist drug candidates for treating PAF-mediated diseases.en_US
dc.identifier.citationNordin Noraziah*, Jalil Juriyati, Ghani Faiz Abd Mohd, Abdullah Afandi Adib and Othman Rozana, Molecular Modelling Simulations and Inhibitory Effects of Naturally Derived Flavonoids Targeting Platelet-Activating Factor Receptor (PAFR), Letters in Drug Design & Discovery 2022; 19(1) . https://dx.doi.org/10.2174/1570180818666210614170322en_US
dc.identifier.doi10.2174/1570180818666210614170322
dc.identifier.epage11
dc.identifier.issn1570-1808
dc.identifier.issue1
dc.identifier.other2169-23
dc.identifier.spage1
dc.identifier.urihttps://www.eurekaselect.com/article/116159
dc.identifier.urihttps://oarep.usim.edu.my/handle/123456789/4166
dc.identifier.volume19
dc.language.isoenen_US
dc.publisherBentham Science Publicationen_US
dc.relation.ispartofLetters in Drug Design & Discoveryen_US
dc.subjectFlavonoids, platelet-activating factor, molecular docking, molecular dynamics simulation, PAF assay, antagonist, PAF receptor.en_US
dc.titleMolecular Modelling Simulations And Inhibitory Effects Of Naturally Derived Flavonoids Targeting Platelet-activating Factor Receptor (pafr)en_US
dc.typeArticleen_US
dspace.entity.typePublication

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