Nagilactones are tetracyclic natural products isolated from various Podocarpus species. These lactone-based compounds display a range of pharmacological effects, including antifungal, anti-atherosclerosis, anti-inflammatory and anticancer activities reviewed here. The most active derivatives, such as nagilactones C, E and F, exhibit potent anticancer activities against different cancer cell lines and tumor models. A comprehensive analysis of their mechanism of action indicates that their anticancer activity mainly derives from three complementary action: (i) a drug-induced inhibition of cell proliferation coupled with a cell cycle perturbation and induction of apoptosis, (ii) a blockade of the epithelial to mesenchymal cell transition contributing to an inhibition of cancer cell migration and invasion and (iii) a capacity to modulate the PD-L1 immune checkpoint. Different molecular effectors have been implicated in the antitumor activity, chiefly the AP-1 pathway blocked upon activation of the JNK/c-Jun axis. Nag-C is a potent inhibitor of protein synthesis binding to eukaryotic ribosomes and inhibition of different protein kinases, such as RIOK2 and JAK2, has been postulated with Nag-E. The literature survey on nagilactones highlights the therapeutic potential of these little-known terpenoids. The mechanistic analysis also provides useful information for structurally related compounds (podolactones, oidiolactones, inumakilactones) isolated from Podocarpus plants.

半乳糖内酯是从各种罗汉松中分离得到的四环天然产物种类。这些基于内酯的化合物具有多种药理作用，包括此处所述的抗真菌，抗动脉粥样硬化，抗炎和抗癌活性。最具活性的衍生物，例如萘丙内酯C，E和F，对不同的癌细胞系和肿瘤模型表现出有效的抗癌活性。对其作用机理的全面分析表明，它们的抗癌活性主要来自三个互补作用：（i）药物诱导的对细胞增殖的抑制，以及细胞周期的扰动和凋亡的诱导，（ii）上皮的阻滞间充质细胞转化为间充质细胞有助于抑制癌细胞的迁移和侵袭，以及（iii）调节PD-L1免疫检查点的能力。不同的分子效应子与抗肿瘤活性有关，主要是AP-1途径在JNK / c-Jun轴激活后被阻断。Nag-C是与真核生物核糖体结合的有效的蛋白质合成抑制剂，Nag-E假定可以抑制不同的蛋白激酶，例如RIOK2和JAK2。关于萘甲内酯的文献调查强调了这些鲜为人知的萜类化合物的治疗潜力。机理分析还提供了有用的信息，可用于从中分离出的结构相关化合物（podolactones，oidiolactones，inumakilactones）。已被假定为Nag-E。关于萘甲内酯的文献调查强调了这些鲜为人知的萜类化合物的治疗潜力。机理分析还提供了有用的信息，可用于从中分离出的结构相关化合物（podolactones，oidiolactones，inumakilactones）。已被假定为Nag-E。关于萘甲内酯的文献调查强调了这些鲜为人知的萜类化合物的治疗潜力。机理分析还提供了有用的信息，可用于从中分离出的结构相关化合物（podolactones，oidiolactones，inumakilactones）。罗汉松植物。