New prenylated indole diketopiperazine alkaloids and polyketides from the mangrove-derived fungus Penicillium sp

Abstract

Two new prenylated indole diketopiperazine alkaloids (PIDAs) penicamides A and B (1 and 2) and three new polyketides penicinones A−C (6−8), along with four known compounds deoxybrevianamide E (3), brevianamide V (4), 12,13-dehydroprolyl-2-(1,1-dimethylallyltryptophyl)diketopiperazine (5), and 4-hydroxyphenethyl 2-(4-hydroxyphenyl)acetate (9), were isolated and identified from the culture extract of the mangrove-derived fungus Penicillium sp. Their structures were fully elucidated by analyzing spectroscopic data. The absolute configurations of these compounds were determined by the comparison of experimental and calculated electronic circular dichroism (ECD) data and Mo2(OAc)4-induced and Rh2(OCOCF3)4-induced ECD experiments. Structurally, compound 1 is the first example of PIDAs featuring a 6/5/8/6/5 pentacyclic ring system with an α-hydroxy group at C-11, while compound 2 is a new analogue of PIDAs possessing the unique 3-methyleneindolin-2-ol moiety. In addition, compound 6 is a new lactone with the furo[3,4-b]pyran-5-one moiety. Compound 6 displayed potent cytotoxicity against murine melanoma (B16) cells, human breast adenocarcinoma (MCF-7) cells, and human hepatocellular carcinoma (HepG2) cells at 50.0 µM with inhibitory ratios of 82.7%, 75.1% and 95.9%, respectively. In addition, compound 6 exhibited significantly cytotoxic activity against the HepG2 cells, with an IC50 value of 3.87 ± 0.74 µM.