**1. Introduction**

There are many natural products isolated from marine-derived fungi. These compounds are important source of biologically effective secondary metabolites, which are very interesting and important for drug discovery. In particular, a large number of natural products with biological activities are found in the genus *Penicillium*, which has diverse biological activities such as antibacterial, antifungal, antitumor, and antiviral activities [1–18]. Diverse dihydroisocoumarins [4], citrinin [15], benzopyrans [17], benzophenones [18] and their derivatives were isolated from *Penicillium citrinum* in the past studies. Many of these isolated compounds showed anti-bacterial [4,17,18], anti-fungal [15], and anti-cancer [18] activities.

Human neutrophils are known to play a critical role in the pathogenesis of various inflammatory diseases [19,20]. In response to different stimuli, activated neutrophils secrete a series of cytotoxins, such as superoxide anion (O2 •–), granule proteases, and bioactive lipids [19,21,22]. Suppression of inappropriate activation of neutrophils by drugs was proposed as a way to combat inflammatory diseases [23].

According to statistics from Taiwan's Ministry of Health and Welfare, cancer remained the top killer in Taiwan for many years [24]. The apoptosis-related proteins, such as Bcl-2,

**Citation:** Chu, Y.-C.; Chang, C.-H.; Liao, H.-R.; Cheng, M.-J.; Wu, M.-D.; Fu, S.-L.; Chen, J.-J. Rare Chromone Derivatives from the Marine-Derived *Penicillium citrinum* with Anti-Cancer and Anti-Inflammatory Activities. *Mar. Drugs* **2021**, *19*, 25. https:// doi.org/10.3390/md19010025

Received: 17 November 2020 Accepted: 5 January 2021 Published: 8 January 2021

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Bax*,* and caspase-3, regulate cancer cell apoptosis or survival, which was confirmed to be related to many cancers and diseases [25–27]. In a preliminary screening, the methanolic extract of *P. citrinum* showed anti-inflammatory and anti-cancer activities in vitro. The current chemical investigation of this fungus led to the isolation of three new chromone derivatives, epiremisporine C (**1**), epiremisporine D (**2**), and epiremisporine E (**3**), along with four known compounds. The structural elucidation of **1**–**3** and anti-inflammatory and anti-cancer properties of **1–7** are described herein.

#### **2. Results and Discussion**

#### *2.1. Fermentation, Extraction, and Isolation*

In this study, the marine-derived fungal strain *Penicillium citrinum* (BCRC 09F0458) was cultured in solid-state culturing conditions, in order to enrich the diversity of the fungal secondary metabolites. Chromatographic isolation and purification of the *n*-BuOH-soluble fraction of an EtOH extract of *Penicillium citrinum* on a silica gel column and preparative thin-layer chromatography (TLC) obtained three new (**1**–**3**) and four known compounds (**4**–**7**) (Figure 1).

**Figure 1.** The chemical structures of compounds **1**–**7** isolated from *Penicillium citrinum*.
