Novel phenalenone derivatives

Marine-derived fungi are an important source of pharmacologically active natural products. Investigation of the crude extract of the fungus Coniothyrium cereale provided a new series of phenalenone derivatives, obtained by HPLC separations. The structures of the compounds were established on the basis of extensive spectroscopic studies (1H; 13C; HSQC, COSY, NOESY and HMBC), mass spectral analysis (LC/MS and HRESIMS), UV and IR. The absolute stereochemistry is based on the specific optical rotation and CD spectra which were compared with published data. Structurally most unusual and unprecedented is the lactame-containing compound 7. The compounds are subjected to cytotoxicity and antimicrobial evaluation and also towards the the enzymes human leukocyte elastase (HLE), trypsin, chymotrypsin, acetylcholinesterase, papain, cholesterolesterase and thrombin. Compounds 6 and 7 showed good in vitro cytotoxicity of IC50=41 and 27µM respectively. Compounds 6 and 8 showed antimicrobial activity of MIC=7.8 and 15.6µg/mL respectively. Compounds 1, 2 and 7 showed potent inhibition of HLE with IC50 values of 7.16, 10.9 and 13.3µM, respectively.

Fig.1: Structures of metabolites isolated from Coniothyrium cereale

Acknowledgements: Financial support from the Egyptian Government and from BMBF (project No. 03F0415A)