Cytochalasan and Tyrosine-Derived Alkaloids from the Marine Sediment-Derived Fungus Westerdykella dispersa and Their Bioactivities

Abstract

Six new cytochalasans, designated as 18-oxo-19,20-dihydrophomacin C (1), 18-oxo-19-methoxy-19,20- dihydrophomacin C (2), 18-oxo-19-hydroxyl-19,20-dihydrophomacin C (3), 19,20-dihydrophomacin C (4), 19-methoxy-19,20-dihydrophomacin C (5), 19-hydroxyl-19,20-dihydrophomacin C (6), and one new tyrosine-derived alkaloid named as gymnastatin Z (8), together with two known compounds, phomacin B (7) and triticone D (9), were isolated from a solid-substrate fermentation culture of Westerdykella dispersa which was derived from marine sediments. Their structures were established on the basis of spectroscopic analysis using 1D and 2D NMR techniques, and comparison of NMR data to those of known compounds. The anti-bacterial and cytotoxic activities assays of all isolated compounds were evaluated against eight human pathogenic bacteria and five human cancer cell lines, respectively. Compound 8 exhibited moderate activity against B. subtilis with MIC values of 12.5 µg/mL, while compounds 5, 7 and 8 displayed moderate inhibitory activities against five human cancer cell lines (MCF-7, HepG2, A549, HT-29 and SGC-7901), with IC₅₀ values ranging from 25.6 to 83.7 µM.

Figure 1

Structures of compounds 1–9.

Figure 2

COSY and selected HMBC correlations of compounds 1–6 and 8.

Figure 3

Key NOESY correlations of compounds 1–6.

Figure 4

X-ray structure of compound 1.

Figure 5

Calculated and experimental ECD spectra of compounds 2–4.