Antimicrobial phenalenone derivatives from the marine-derived fungus Coniothyrium cereale

The marine-derived fungus Coniothyrium cereale was isolated from the green alga Enteromorpha sp. and found to produce the new phenalenone derivatives 1-7 as well as the known compounds lactone 8, (-) sclerodin (9), lamellicolic anhydride (10), (-) scleroderolide (11), and (-) sclerodione (12). The structures of these closely related compounds were established from extensive spectroscopic investigations on the basis of one and two dimensional NMR spectroscopic studies (H-1, C-13, COSY, NOESY, HSQC and HMBC) as well as mass spectrometric analysis (LC/MS, HREIMS and HRESIMS), UV and IR spectra. Compounds 5 and 11 showed the same antimicrobial activity toward Staphylococcus aureus SG 511 with an MIC value of 24 mu M. The presence of a diketo-lactone ring as in compounds 5 and 11 was found to be essential for this activity. In agar diffusion assays with Mycobacterium phlei considerable inhibition zones were observed for compounds 2, 4 and 7. Compounds 1, 5 and 9 showed potent inhibition of human leukocyte elastase (HLE) with IC50 values of 7.2, 13.3 and 10.9 mu M, respectively.