New Deoxyisoaustamide Derivatives from the Coral-Derived Fungus Penicillium dimorphosporum KMM 4689

Abstract

Seven new deoxyisoaustamide derivatives (1-7) together with known compounds (8-10) were isolated from the coral-derived fungus Penicillium dimorphosporum KMM 4689. Their structures were established using spectroscopic methods, X-ray diffraction analysis and by comparison with related known compounds. The absolute configurations of some alkaloids were determined based on CD and NOESY data as well as biogenetic considerations. The cytotoxic and neuroprotective activities of some of the isolated compounds were examined and structure-activity relationships were pointed out. New deoxyisoaustamides 4-6 at concentration of 1 µM revealed a statistical increase of PQ(paraquat)-treated Neuro-2a cell viability by 30-39%.

Keywords: Penicillium dimorphosporum; deoxyisoaustamide; neuroprotective activity; paraquat; prenylated indole diketopiperazines; secondary metabolites.

Figure 1

Chemical structures of 1–10.

Figure 2

X-ray crystallographic structure of compound 1.

Figure 3

Key COSY and HMBC correlations of 2 and 3.

Figure 4

(a) CD spectra of 2(blue) and 5(red); (b) CD spectra of 3(blue) and 6(red).

Figure 5

Effects of compounds 1–10 on viability of PQ (paraquat)-treated Neuro-2a cells. Each bar represents the mean ± SEM of three independent replicates. (*) indicate p < 0.05 versus PQ-treated cells. The difference between control and PQ-treated cells was significant (p < 0.05).