Penrhizovarin A, a novel indole diterpene from endophytic fungi Penicillium sp. KYG-9

One novel indole diterpene penrhizovarin A (1) and one known analogue (2), were characterized from Penicillium sp. KYG-9. Structural elucidation was accomplished through comprehensive spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), X-ray crystallography, and electronic circular dichroism (ECD) calculations. Penrhizovarin A (1) is the first reported indole diterpene characterized by both an unprecedented F-ring cleavage and a novel 4/6/6/6/5–6/6/6 pentacyclic scaffold incorporating a rare dioxabicyclo[3.3.1]nonane unit. The single crystal of 2 was obtained for the first time, and its planar structure and stereochemistry were further confirmed by X-ray single crystal diffraction. In vitro bioassays revealed that penrhizovarin A exhibited potent cytotoxicity against all tested human cancer cell lines, with particularly notable activity against HL-60 (leukemia), A-549 (lung cancer), and SW-480 (colon cancer) cell lines, surpassing the activity of the positive control cisplatin. Additionally, penrhizovarin A demonstrated significant antifungal activities.