Wakselman M, Cerutti I, Chany C
C.N.R.S.-C.E.R.C.O.A, Thiais, France.
Int J Cancer. 1990 Sep 15;46(3):462-7. doi: 10.1002/ijc.2910460323.
Simple fatty acids, especially butyrate salts, have interesting biological properties, since they are able to down-regulate cell growth and promote various differentiated cellular functions. Their use for anti-tumor treatment is, however, hampered by their over-rapid diffusion in the blood, followed by a short-lived biological action. We have therefore devised conjugates linking butyrate with either (i) aliphatic alcohols of increasing carbon numbers ranging from C4 to C12 or (ii) poly(ethylene glycols) of increasing molecular weights. In both cases, the resulting butyric esters can be hydrolysed by esterases which can release biologically active subunits from the synthetic compounds. As shown in the present study, only one conjugate in each series gave satisfactory anti-tumor protection: namely, I-octyl butyrate and poly(ethylene glycol 1000) dibutyrate respectively. A single immune-stimulatory injection of purified Corynebacterium parvum extract prior to administration of the conjugates significantly increased the anti-tumor potency.
简单脂肪酸，尤其是丁酸盐，具有有趣的生物学特性，因为它们能够下调细胞生长并促进各种分化的细胞功能。然而，它们在血液中的过快扩散以及随后短暂的生物活性，阻碍了它们在抗肿瘤治疗中的应用。因此，我们设计了将丁酸盐与以下两种物质连接的共轭物：（i）碳数从C4到C12递增的脂肪醇，或（ii）分子量递增的聚乙二醇。在这两种情况下，生成的丁酸酯都可以被酯酶水解，酯酶能够从合成化合物中释放出生物活性亚基。如本研究所示，每个系列中只有一种共轭物具有令人满意的抗肿瘤保护作用：分别是丁酸正辛酯和聚乙二醇1000二丁酸酯。在施用共轭物之前，单次免疫刺激注射纯化的微小棒状杆菌提取物可显著提高抗肿瘤效力。
