Helvamide, a new inhibitor of sterol O-acyltransferase produced by the fungus Aspergillus nidulans BF-0142.

A new piperazine derivative designated helvamide was isolated as a pair of rotamers (1 and 2) from the culture broth of the fungus Aspergillus nidulans BF-0142 along with a known helvafuranone (3). The structures of 1 and 2 were elucidated based on spectroscopic analyses by the interpretation of one-dimensional and two-dimensional nuclear magnetic resonance data, ROESY (rotational Overhauser effect spectroscopy) correlations, and a chemical method. Helvamide existed as a rotameric mixture (1 and 2) in dimethyl sulfoxide. Helvamide inhibited sterol O-acyltransferases 1 and 2 (SOAT1 and SOAT2) in enzyme-based and cell-based assays using SOAT1-expressing and SOAT2-expressing Chinese hamster ovary (CHO) cells.