Characterization of Bioactive Compounds from the Red Sea Tunicate-Derived Fungus Penicillium commune DY004

As a part of our ongoing interest to identify bioactive microbial secondary metabolites, the Red Sea tunicate derived Penicillium commune DY004 was investigated. A new dipeptide, penicillizine A (1) together with cyclo(L-Pro-L-Phe) (2), meleagrin (3), alpha-cyclopiazonic acid (4) and N-(4-hydroxyphenethyl)acetamide (5) was isolated from the ethyl acetate extract of the cultures of the fungus. The structural determinations of 1-5 were supported by interpretation of their one and two-dimensional nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. In the evaluation of the compounds for their effects against three human tumorous cell lines, meleagrin (3) and alpha-cyclopiazonic acid (4) displayed the highest and potent activity against HeLa, U373 glioblastoma and MDA-MB-231 cell lines down up to 3.1 mu g/mL. These results suggest that marine fungi are a copious source of drug leads with therapeutic potential. Meleagrin and alpha-cyclopiazonic acid could be used as potential scaffolds for the development of new and more effective drug leads.