Peniapyrones A-I, Cytotoxic Tricyclic-Fused α-Pyrone Derivatives from an Endophytic Penicillium brefeldianum F4a.

Five cyclopenta[ d ]pyrano[4,3- b ]pyran-1,7(6 H )-dione 6/6/5-fused tricyclic ring system containing metabolites peniapyrones A-E ( 1 - 5 ), and four previously undescribed cyclopenta[4,5]furo[3,2- c ]pyran-1-one 6/5/5-fused tricyclic ring system containing compounds peniapyrones F-I ( 6 - 9 ), were isolated from the endophytic Penicillium brefeldianum F4a. Their structures, including absolute configurations, were determined through spectroscopic analysis and quantum chemical calculations. Peniapyrones D ( 4 ) and E ( 5 ) were a pair of diastereoisomers. Compounds 1 , 3 , and 5 - 9 showed cytotoxic activity against AsPC-1, CRL-2234, and MCF-7 cancer cell lines. Compounds 1 , 3 , 6 , 8 , and 9 inhibited the Kirsten rat sarcoma viral oncogene homologue (KRAS) mutant AsPC-1 cell line.