Marine-derived fungi proved to be a rich source of biologically active compounds. The genus Penicillium has been extensively studied regarding their secondary metabolites and biological applications. However, the photoprotective effects of these metabolites remain underexplored. Herein, the photoprotective potential of Penicillium echinulatum, an Antarctic alga-associated fungus, was assessed by UV absorption, photostability study, and protection from UVA-induced ROS generation assay on human immortalized keratinocytes (HaCaT) and reconstructed human skin (RHS). The photosafety was evaluated by the photoreactivity (OECD TG 495) and phototoxicity assays, performed by 3T3 neutral red uptake (3T3 NRU PT, OECD TG 432) and by the RHS model. Through a bio-guided purification approach, four known alkaloids, (-)-cyclopenin (1), dehydrocyclopeptine (2), viridicatin (3), and viridicatol (4), were isolated. Compounds 3 and 4 presented absorption in UVB and UVA-II regions and were considered photostable after UVA irradiation. Despite compounds 3 and 4 showed phototoxic potential in 3T3 NRU PT, no phototoxicity was observed in the RHS model (reduction of cell viability < 30%), which indicates their very low acute photoirritation and high photosafety potential in humans. Viridicatin was considered weakly photoreactive, while viridicatol showed no photoreactivity; both compounds inhibited UVA-induced ROS generation in HaCaT cells, although viridicatol was not able to protect the RHS model against UVA-induced ROS production. Thus, the results highlighted the photoprotective and antioxidant potential of metabolites produced by P. echinulatum which can be considered a new class of molecules for photoprotection, since their photosafety and non-cytotoxicity were predicted using recommended in vitro methods for topical use.

海洋来源的真菌被证明是生物活性化合物的丰富来源。属青霉已被广泛研究关于他们的次生代谢产物和生物应用。然而，这些代谢物的光保护作用仍未得到充分探索。在此，Penicillium echinulatum的光保护潜力南极藻相关真菌，通过紫外线吸收、光稳定性研究和对人类永生化角质形成细胞 (HaCaT) 和重建的人类皮肤 (RHS) 的 UVA 诱导的 ROS 生成试验的保护进行了评估。光安全性通过光反应性 (OECD TG 495) 和光毒性测定进行评估，通过 3T3 中性红吸收 (3T3 NRU PT, OECD TG 432) 和 RHS 模型进行。通过生物引导纯化方法，分离出四种已知的生物碱，(-)-cycloopenin (1)、dehydrocyclopeptine (2)、viridicatin (3) 和 viridicatol (4)。化合物 3 和 4 在 UVB 和 UVA-II 区域有吸收，在 UVA 照射后被认为是光稳定的。尽管化合物 3 和 4 在 3T3 NRU PT 中显示出光毒性潜力，但在 RHS 模型中未观察到光毒性（细胞活力降低 < 30%），这表明它们对人类的急性光刺激性非常低，并且具有很高的光安全潜力。Viridicatin 被认为是弱光反应性的，而 viridicatol 没有表现出光反应性。两种化合物都抑制了 HaCaT 细胞中 UVA 诱导的 ROS 生成，尽管绿草醇不能保护 RHS 模型免受 UVA 诱导的 ROS 生成。因此，结果强调了由以下物质产生的代谢物的光保护和抗氧化潜力P. echinulatum可以被认为是一类新的光保护分子，因为它们的光安全性和非细胞毒性是使用推荐的局部使用体外方法预测的。