Abstract

Genus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3β,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC₅₀ values of 2.89, 18.51, and 16.47 µg/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37 ± 1.35% at 25 µg/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

摘要

青霉菌属是最重要和最广泛研究的真菌，作为次生代谢物的丰富来源而闻名。我们的研究旨在分析和研究来自海洋的P. levitum真菌代谢物的生物活性，包括体外抗癌、抗炎和抗糖尿病特性。用乙酸乙酯提取P. levitum菌株N33.2培养液中的化学成分。随后，对提取物进行化学分析，分离出三种麦角甾烷型类固醇成分，即 cerevisterol (1)、过氧化麦角甾醇(2)和 (3β,5α,22E)-ergosta-6,8(14),22 -三烯-3,5-二醇(3)。其中，(3)对人癌细胞系 Hep-G2、A549 和 MCF-7 具有最强的细胞毒性，IC ₅₀值分别为 2.89、18.51 和 16.47 µg/mL，而化合物(1)没有显示出对人癌细胞的抑制作用。对测试的癌细胞有显着效果。根据 LPS 诱导的鼠 RAW264.7 巨噬细胞中 NO 的产生来评估纯化化合物的抗炎特性。结果，受试化合物对巨噬细胞产生NO具有不同的抑制作用，其中化合物(2)在25μg/mL时的抑制率最显着，为81.37±1.35 %。有趣的是，化合物（2）和（3）在体外试验中表现出对胰腺脂肪酶和α-葡萄糖苷酶的抑制活性。我们的研究得出了有关从P. levitum真菌中分离出的类固醇的化学性质和生物活性的新数据。