Rare Glutamic Acid Methyl Ester Peptaibols from Damon KSH 534 Exhibit Promising Antifungal and Anticancer Activity.

Fungal species of genus are rich sources of diverse secondary metabolites (e.g., alkaloids, peptaibols), which exhibit variable biological activities. Herein, two new peptaibols, named ampullosporin F () and ampullosporin G (), together with five known compounds, ampullosporin A (), peptaibolin (), chrysosporide (), c(Trp-Ser) () and c(Trp-Ala) (), have been isolated from the culture of Damon strain KSH534. The structures of and were elucidated based on ESI-HRMS experiments and intense 1D and 2D NMR analyses. The sequence of ampullosporin F () was determined to be Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-GluOMe-Leu-Aib-Gln-Leuol, while ampullosporin G () differs from by exchanging the position of Gln with GluOMe. Furthermore, the total synthesis of and was carried out on solid-phase to confirm the absolute configuration of all chiral amino acids as L. In addition, ampullosporin F () and G () showed significant antifungal activity against and , but were inactive against . Cell viability assays using human prostate (PC-3) and colorectal (HT-29) cancer cells confirmed potent anticancer activities of and . Furthermore, a molecular docking study was performed in silico as an attempt to explain the structure-activity correlation of the characteristic ampullosporins (-).