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

Abstract

In the search for antiviral cyclopeptides against influenza A virus, five unprecedented Caryophyllaceae-type cyclopeptides (<b>1</b>-<b>5</b>) were isolated from the leaves of <i>Melicope pteleifolia</i>. 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 <b>3</b>-<b>5</b> 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 (<b>1</b>-<b>5</b>) 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 <b>3</b> 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.