Hordatine A

Hordatine A
Names
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
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
KEGG
UNII
  • InChI=1S/C28H38N8O4/c29-27(30)35-15-3-1-13-33-23(38)12-6-18-5-11-22-21(17-18)24(25(40-22)19-7-9-20(37)10-8-19)26(39)34-14-2-4-16-36-28(31)32/h5-12,17,24-25,37H,1-4,13-16H2,(H,33,38)(H,34,39)(H4,29,30,35)(H4,31,32,36)/b12-6+/t24-,25+/m0/s1
    Key: KVYNYRIOAYQBFK-AIIPJEMGSA-N
  • glucoside: InChI=1S/C34H48N8O10/c35-33(36)41-13-3-1-11-39-24(45)10-5-18-15-21-25(31(49)40-12-2-4-14-42-34(37)38)29(52-30(21)22(44)16-18)19-6-8-20(9-7-19)50-32-28(48)27(47)26(46)23(17-43)51-32/h5-10,15-16,23,25-29,32,43-44,46-48H,1-4,11-14,17H2,(H,39,45)(H,40,49)(H4,35,36,41)(H4,37,38,42)/b10-5-
  • C1=CC(=CC=C1[C@@H]2[C@H](C3=C(O2)C=CC(=C3)/C=C/C(=O)NCCCCN=C(N)N)C(=O)NCCCCN=C(N)N)O
  • glucoside: C1=CC(=CC=C1C2C(C3=C(O2)C(=CC(=C3)C=CC(=O)NCCCCN=C(N)N)O)C(=O)NCCCCN=C(N)N)OC4C(C(C(C(O4)CO)O)O)O
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).
Infobox references

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] It, along with its cis-isomer aperidine, has been found to activate the muscarinic M3 receptor; this mechanism is thought to contribute to the increase in GI motility caused by beer consumption.[4]

Biosynthesis

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.[5][6] 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.[7]

Biosynthesis of hordatine A, where ACT = agmatine coumaroyltransferase, CoASH = coenzyme A.

Function

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.[8]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ Yamaji, Nahoko; Yokoo, Yoshiaki; Iwashita, Takashi; Nemoto, Asuka; Koike, Minako; Suwa, Yoshihide; Wakimoto, Toshiyuki; Tsuji, Kuniro; Nukaya, Haruo (January 2007). "Structural Determination of Two Active Compounds That Bind to the Muscarinic M 3 Receptor in Beer". Alcoholism: Clinical and Experimental Research. 31 (s1). doi:10.1111/j.1530-0277.2006.00280.x. ISSN 0145-6008.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ ""PubChem Compound Summary for CID 131751024, Hordatine A glucoside"". National Center for Biotechnology Information. PubChem. Retrieved 30 May 2022.
  8. ↑ 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.
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