Hordatine A
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IUPAC name
(2S,3S)-N-[4-(Diaminomethylideneamino)butyl]-5-[(E)-3-[4-(diaminomethylideneamino)butylamino]-3-oxoprop-1-enyl]-2-(4-hydroxyphenyl)-2,3-dihydro-1-benzofuran-3-carboxamide
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Identifiers | |
3D model (JSmol)
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ChEBI | |
ChEMBL | |
ChemSpider | |
KEGG | |
PubChem CID
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CompTox Dashboard (EPA)
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Properties | |
C28H38N8O4 | |
Molar mass | 550.664 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Hordatine A is a phenolic secondary metabolite and an adrenergic antagonist that is found in barley. This natural product is a member of the class benzofurans, and can also be found in barley malt and beer, as it withstands moderate processing.[1] Hordatine A is a hydroxycinnamic acid amide derivative (HCAA) as well as a dimer of coumaroyl agmatine, and is plentiful during the development of barley seedlings, specifically in the shoots.[2] Hordatines and their hydroxycinnamoyl agmatine precursors are of interest because of their antifungal activity against plant pathogens, such as inhibiting spore germination of many fungi species. Hordatine A is thought to be a phytoanticipin, because it is observed in significant amounts in young seedlings and at early growth stages.[3]
Biosynthesis
[edit]The first step in the biosynthesis of hordatine A is characterized by the use of the enzyme agmatine coumaroyltransferase (ACT), which catalyzes the formation of p-coumaroylagmatine from p-coumaroyl-CoA and agmatine. The second step in the biosynthesis of the natural product is characterized by the oxidative coupling of two molecules of p-coumaroylagmatine by the enzyme peroxidase.[4][5] The formation of this homodimer and its observable furan ring results from the hydroxy group of one p-coumaroylagmatine molecule reacting with the ethylene double bond of the other molecule.[6]
Function
[edit]Hordatine A and hordatine B are potential inhibitors of COVID-19 main protease and RNA polymerase, and could serve as potential therapeutic drugs against COVID-19. Hordatine A has been found to overcome activity of key targets of COVID-19, the first being the protease 7BQY and the second being the RNA polymerase 7bV2. Out of multiple target compounds found to possess binding affinities to these targets, hordatine A and hordatine B were found to not only have the highest binding affinity but to also have a higher binding affinity than the native ligand in RNA polymerase, Remdesivir. This is due to the substantial interaction of Hordatine A and B with varying receptor-binding residues, as well as the hydrogen bond formation of Hordatines to catalytic residues.[7]
References
[edit]- ^ Pihlava, Juha-Matti; Tuula, Kurtelius; Timo, Hurme (2016). "Total Hordatine Content in Different Types of Beer". Journal of the Institute of Brewing. 122 (2). WIley Online Library: 212–217. doi:10.1002/jib.311.
- ^ Dahab, Mohammed; Hegazy, Mostafa; Abbass, Hatem (2020). "Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach". Natural Products and Bioprospecting. 10 (6). PMC PubMed Central: 453–462. doi:10.1007/s13659-020-00275-9. PMC 7579552. PMID 33090359.
- ^ Hamany Djande, Claude Y.; Steenkamp, Paul A.; Piater, Lizelle A.; Tugizimana, Fidele; Dubery, Ian A. (2022). "Hordatines and Associated Precursors Dominate Metabolite Profiles of Barley (Hordeum vulgare L.) Seedlings: A Metabolomics Study of Five Cultivars". Metabolites. 12 (4). PMC PubMed Central: 310. doi:10.3390/metabo12040310. PMC 9030721. PMID 35448497.
- ^ Nomura, Taiji; Ishizuka, Akihiro; Kishida, Kazunori; Islam, A.K.M. Rafiqul; Endo, Takashi; Iwamura, Hajime; Ishihara, Atsushi (2007). "Chromosome arm location of the genes for the biosynthesis of hordatines in barley". Genes & Genetic Systems. 82 (6): 455–464. doi:10.1266/ggs.82.455. PMID 18270436. S2CID 23698979.
- ^ Hamany Djande, Claude Y.; Steenkamp, Paul A.; Piater, Lizelle A.; Tugizimana, Fidele; Dubery, Ian A. (2022). "Hordatines and Associated Precursors Dominate Metabolite Profiles of Barley (Hordeum vulgare L.) Seedlings: A Metabolomics Study of Five Cultivars". Metabolites. 12 (4). PMC PubMed Central: 310. doi:10.3390/metabo12040310. PMC 9030721. PMID 35448497.
- ^ ""PubChem Compound Summary for CID 131751024, Hordatine A glucoside"". National Center for Biotechnology Information. PubChem. Retrieved 30 May 2022.
- ^ Dahab, Mohammed; Hegazy, Mostafa; Abbass, Hatem (2020). "Hordatines as a Potential Inhibitor of COVID-19 Main Protease and RNA Polymerase: An In-Silico Approach". Natural Products and Bioprospecting. 10 (6). PMC PubMed Central: 453–462. doi:10.1007/s13659-020-00275-9. PMC 7579552. PMID 33090359.