posted on 2020-03-19, 19:22authored byMarco Masi, Alessio Cimmino, Flora Salzano, Roberta Di Lecce, Marcin Górecki, Viola Calabrò, Gennaro Pescitelli, Antonio Evidente
Two new diterpenoids with tetrasubstituted
3-oxodihydrofuran substituents,
named higginsianins D (1) and E (2), were
isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as methyl 2-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)-decahydronaphthalen-1-ylmethyl]-4,5-dimethyl-3-oxo-2,3-dihydrofuran-2-carboxylate
and its 21-epimer by using NMR, HRESIMS, and chemical methods. The
relative configurations of higginsianins D and E, which did not afford
crystals suitable for X-ray analysis, were determined by NOESY experiments
and by comparison with NMR data of higginsianin B. The absolute configuration
was established by comparison of experimental and calculated electronic
circular dichroism data. The evaluation of 1 and 2 for antiproliferative activity against human A431 cells
derived from epidermoid carcinoma and H1299 non-small-cell lung carcinoma
cells revealed that 2 exhibited higher cytotoxic activity
than 1, with an IC50 value of 1.0 μM
against A431 cells. Remarkably, both 1 and 2 were almost ineffective against immortalized keratinocytes, used
as a preneoplastic cell line model.