New cytochalasan alkaloids and neuroactive communesins from marine-derived Penicillium expansum Link

Terrestrial micromycetes are the source of various active metabolites like antibiotic, cytotoxic, neurotoxic or immunosuppressive substances. The study of marine-derived fungi is relatively recent, but the discovery of numerous new substances demonstrates that they represent a promising source of original natural products [1]. Within the framework of increasing numbers of neurological pathologies, there is a pressing need for new drugs on neurological targets.

In this context, bioactivity screening has been performed on ethyl acetate/CH₂Cl₂ crude extracts of saprotrophic fungal strains, isolated from marine sediments [2]. Neuroactivity assessment was carried out by injection on blowfly larvae [3] and cytotoxicity was evaluated by MTT assay on KB cell line. The extract of a Penicillium expansum strain, cultured on solid seawater DCA medium, exhibited an interesting activity with a rapid paralytic contraction of larvae and an IC₅₀=14.7µg/mL on KB cells. Bio-guided fractionation of this extract was performed, including different steps of liquid chromatography and purification by C₁₈ RP-HPLC. Isolated compounds were analysed by spectroscopic methods (ESI-IT/MS, HR-MS, and ¹H, ¹³C-NMR) and identified as indole alkaloids, the known communesin B together with a new derivative, which structure elucidation is currently under process. Beside communesins, compounds belonging to the cytochalasan alkaloids have been observed in other fractions. They were identified as isomers of chaetoglobosin A (i.e. B, C, D or G) already described in P. expansum [4], and a novel methoxy derivative; these compounds showed weak cytotoxicity (22.0 to 48.0µg/mL). Communesin B exhibited a neuroactivity on blowfly larvae with a minimal active concentration of 0.2µg/mL.

References: 1. Bugni, T.S., Ireland, C.M. (2004) Nat. Prod. Rep. 21: 143–163 2. Sallenave-Namont, C. et al. (2000) Mycopathologia 149: 21–25 3. Zlotkin, E. et al. (1971) Toxicon 9: 1–8 4. Andersen, B. et al. (2004)J. Agric. Food Chem. 52: 2421–2428.