Conditional changes enhanced production of bioactive metabolites of marine derived fungus Eurotium rubrum
- Bioorg Med Chem Lett. 2016 Oct 15;26(20):4911-4914. doi: 10.1016/j.bmcl.2016.09.017.
- 1. Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-shi, Tokyo 204-8588, Japan.
- 2. Department of Microbiology, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-shi, Tokyo 204-8588, Japan.
- 3. Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-shi, Tokyo 204-8588, Japan. Electronic address: [email protected].
Metabolites of marine derived fungus Eurotium rubrum MPUC136 differed between cultivation on wheat medium and Czapek-Dox agar medium. Melanin synthesis inhibitory activity of crude extract of culture on wheat medium showed stronger activity than that of crude extract of culture on Czapek-Dox agar medium. A new diketopiperazine compound isoechinulin D (1) and eight reported diketopiperazines (2-9) were isolated from the crude extract of wheat medium. The structure of 1 was established using NMR, MS and IR methods. 2-5 inhibited melanogenesis using B16 melanoma cells (IC50=68, 2.4, 83, 9.1μM each). Structure-Activity-Relationships of diketopiperazines (1-10) indicated the importance of the prenyl groups at C-2, C-5 and C-7, the vinyl group at C-12 to C-25 and the sp2 carbons at C-8 and C-9. Isolated compounds (1-9) were not or slightly observed from the extracts of Czapek-Dox agar medium by HPLC analysis, suggesting that different cultivation processes could affect metabolism and enhance bioactivities.