Fundación MEDINA, Av. Conocimiento 34, Health Sciences Technology Park, 18016 Granada, Spain.
Molecules. 2024 Jan 15;29(2):425. doi: 10.3390/molecules29020425.
Cancer is one of the leading causes of death worldwide, with breast cancer being the second cause of cancer-related mortality among women. Natural Products (NPs) are one of the main sources for drug discovery. During a screening campaign focused on the identification of extracts from Fundación MEDINA's library inhibiting the proliferation of cancer cell lines, a significant bioactivity was observed in extracts from cultures of the fungus CF-097565. Bioassay-guided fractionation of this extract led to the identification and isolation of herbarin (), 1-hydroxydehydroherbarin () plus other three naphthoquinone derivatives of which and are new natural products and is herein described from a natural source for the first time. Four of these compounds (, , and ) confirmed a specific cytotoxic effect against the human breast cancer cell line MCF-7. To evaluate the therapeutic potential of the compounds isolated, their efficacy was validated in 3D cultures, a cancer model of higher functionality. Additionally, an in-depth study was carried out to test the effect of the compounds in terms of cell mortality, sphere disaggregation, shrinkage, and morphology. The cell profile of the compounds was also compared to that of known cytotoxic compounds with the aim to distinguish the drug mode of action (MoA). The profiles of , and showed more biosimilarity between them, different to , and even more different to other known cytotoxic agents, suggesting an alternative MoA responsible for their cytotoxicity in 3D cultures.
癌症是全球主要死因之一，乳腺癌是女性癌症相关死亡的第二大原因。天然产物（NPs）是药物发现的主要来源之一。在一项针对鉴定 Fundación MEDINA 文库提取物抑制癌细胞系增殖的筛选活动中，从真菌 CF-097565 的培养物中观察到了显著的生物活性。对该提取物进行生物活性导向分离，鉴定并分离出了 Herbarin（）、1-羟基脱氢 Herbarin（）和其他三种萘醌衍生物，其中和是新的天然产物，是首次从天然来源中描述的。这四种化合物（、、和）证实对人乳腺癌细胞系 MCF-7 具有特异性细胞毒性作用。为了评估分离化合物的治疗潜力，在 3D 培养物中验证了它们的功效，3D 培养物是一种具有更高功能的癌症模型。此外，还进行了深入研究，以测试化合物在细胞死亡率、球体解聚、收缩和形态方面的作用。还将化合物的细胞特征与已知的细胞毒性化合物进行了比较，目的是区分药物作用模式（MoA）。、和的化合物特征显示出它们之间的生物相似性更高，与不同，甚至与其他已知的细胞毒性剂更不同，这表明它们在 3D 培养物中的细胞毒性作用有替代的 MoA。
