Penisimplinoids A-K, Highly Oxygenated Andrastin-Type Meroterpenoids with Diverse Activities from the Marine-Derived Fungus Penicillium Simplicissimum.

Penisimplinoid A (1), the first andrastin-type meroterpenoid with an unprecedented 6/6/3/6/5/5 polycyclic systems, together with ten highly oxygenated andrastin-type meroterpenoids (2-11) and one known analogue (12), were co-isolated from the marine-derived fungus Penicillium simplicissimum. Their absolute configurations were determined by single-crystal X-ray diffraction analysis (Cu Kα), DP4+ probability analyses, and ECD quantum chemistry calculations. Biological evaluation revealed that 7 and 12 showed anti-inflammatory activities in the zebrafish assay, 6 exhibited cytotoxic activity against NCI-H446 tumor cells with an IC50 value of 6.49 μM, 7 and 11 exhibited significant promoting angio-genesis activities.