*Article* **Cytotoxic Indole-Diterpenoids from the Marine-Derived Fungus** *Penicillium* **sp. KFD28**

**Lu-Ting Dai 1, Li Yang 2, Fan-Dong Kong 3, Qing-Yun Ma 2, Qing-Yi Xie 2, Hao-Fu Dai 4, Zhi-Fang Yu 1,\* and You-Xing Zhao 2,\***


**Abstract:** Four new indole-diterpenoids, named penerpenes K-N (**1**–**4**), along with twelve known ones (**5**–**16**), were isolated from the fermentation broth produced by adding L-tryptophan to the culture medium of the marine-derived fungus *Penicillium* sp. KFD28. The structures of the new compounds were elucidated extensively by 1D and 2D NMR, HRESIMS data spectroscopic analyses and ECD calculations. Compound **4** represents the second example of paxilline-type indole diterpene bearing a 1,3-dioxepane ring. Three compounds (**4**, **9,** and **15**) were cytotoxic to cancer cell lines, of which compound **9** was the most active and showed cytotoxic activity against the human liver cancer cell line BeL-7402 with an IC50 value of 5.3 μM. Moreover, six compounds (**5**, **7**, **10**, **12**, **14**, and **15**) showed antibacterial activities against *Staphylococcus aureus* ATCC 6538 and *Bacillus subtilis* ATCC 6633.

**Keywords:** marine-derived fungus; *Penicillium* sp.; indole-diterpenoids; cytotoxicity; antibacterial activity
