Melicopteline A–E, Unusual Cyclopeptide Alkaloids with Antiviral Activity against Influenza A Virus from Melicope pteleifolia

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.