Three N-metallocenoylsphingosines with variance in the central metal (Fe, Co, Ru), the charge (neutral or cationic), and the arene ligands (Cp₂, Cp*Ph) were synthesized from serine and metallocene carboxylic acids as substrate-analogous inhibitors of human acid ceramidase (AC). Their inhibitory potential was examined using the recombinant full length ASAH1 enzyme, expressed and secreted from High Five insect cells, and the fluorescent substrate Rbm14-12. All complexes inhibited AC, most strongly so ruthenium(II) complex 13a. Some antitumoral effects of the complexes, such as the interference with the microtubular and F-actin cytoskeleton of cancer cells, were correlated to their AC-inhibition, whereas others, e.g. their cytotoxicity and their induction of caspase-3/-7 activity in cancer cells, were not. All complexes accumulated preferentially in the lysosomes of cancer cells like their target AC, arrested the cells in G1 phase of the cell cycle, and displayed cytotoxicity with mostly single-digit micromolar IC₅₀ values while inducing cancer cell apoptosis.

以丝氨酸和茂金属羧酸为底物类似物，合成了三种中心金属（Fe，Co，Ru），电荷（中性或阳离子性）和芳烃配体（Cp ₂，Cp * Ph）具有变化的N-茂金属鞘氨醇。人酸性神经酰胺酶（AC）的抑制剂。使用从高等五类昆虫细胞表达和分泌的重组全长ASAH1酶和荧光底物Rbm14-12检查了它们的抑制潜力。所有复合物均抑制AC，最强烈的是钌（II）复合物13a。复合物的一些抗肿瘤作用，例如干扰癌细胞的微管和F-肌动蛋白细胞骨架，与它们的AC抑制作用相关，而其他作用，例如，它们的细胞毒性和对癌症中caspase-3 / -7活性的诱导作用细胞，不是。所有复合物都优先在癌细胞的溶酶体中像它们的靶AC一样积累，将细胞停滞在细胞周期的G1期，并在诱导癌细胞凋亡的同时以单数个微摩尔IC ₅₀值显示出细胞毒性。