Melicopteline A-E, Unusual Cyclopeptide Alkaloids with Antiviral Activity against Influenza A Virus from Melicope pteleifolia.
J Org Chem
; 86(2): 1437-1447, 2021 01 15.
Article
in En
| MEDLINE
| ID: mdl-33369410
ABSTRACT
In the search for antiviral cyclopeptides against influenza A virus, five unprecedented Caryophyllaceae-type cyclopeptides (1-5) were isolated from the leaves of Melicope pteleifolia. Their chemical structures and absolute configurations were unambiguously determined by means of advanced Marfey's analysis and comprehensive spectroscopic analyses including two-dimensional nuclear magnetic resonance and MS/MS fragmentation. Interestingly, compounds 3-5 contain an unusual heterocycle, a 3a-hydroxypyrroloindole moiety, which was biosynthetically formed by a nucleophilic cyclization from the least abundant amino acid, tryptophan, precursor and has aroused a great interest in the aspect of chemical diversity and biological activity. All isolates (1-5) were evaluated for their protective effects against influenza A viruses H1N1 and H9N2 in MDCK cells. All isolated cyclopeptides exhibited strong anti-influenza activity, especially against H1N1. Compound 3 showed the most potent CPE inhibition effect, which was stronger than that of the positive control ribavirin against H1N1, with an EC50 (µM) of 2.57 ± 0.45 along with higher selectivity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Rutaceae
/
Alkaloids
/
Influenza A Virus, H1N1 Subtype
/
Influenza A Virus, H9N2 Subtype
Language:
En
Journal:
J Org Chem
Year:
2021
Document type:
Article