Sasaki T, Yamakoshi J, Saito M, Kasai K, Matsudo T, Kikuchi M, Koga T, Mori K
Research and Development Division, Kikkoman Corporation, Chiba, Japan.
Biosci Biotechnol Biochem. 1998 Nov;62(11):2145-54. doi: 10.1271/bbb.62.2145.
4-Hydroxy-2,5-dimethyl-3(2H)-furanone (HDMF) and 2(or 5)-ethyl-4-hydroxy-5(or 2)-methyl-3(2H)-furanone (EHMF) are known to inhibit cataract development in spontaneous cataract rats (ICR/f). Forty-five acylated hydroxyfuranone derivatives were designed and synthesized for an anti-cataract test, and their hydrophobic constants were also tested. Among these derivatives, 2,5-dimethyl-4-pivaloyloxy-3(2H)-furanone (HDMF pivalate) exerted a marked protective effect against the development of cataract in a galactose-induced model using cultured rat lens (in vitro). When tested on an ICR/f cataract model (in vivo), HDMF pivalate showed more significant inhibition of cataract development than parent compound HDMF. This derivative is more lipophilic than HDMF, so that HDMF pivalate can penetrate the cornea more easily than HDMF. The inhibition of cataract development by HDMF converted from HDMF pivalate is supported by the fact that HDMF was observed in the lens of ICR/f rats treated with HDMF pivalate.
已知4-羟基-2,5-二甲基-3（2H）-呋喃酮（HDMF）和2（或5）-乙基-4-羟基-5（或2）-甲基-3（2H）-呋喃酮（EHMF）可抑制自发性白内障大鼠（ICR/f）的白内障发展。设计并合成了45种酰化羟基呋喃酮衍生物用于抗白内障试验，并测试了它们的疏水常数。在这些衍生物中，2,5-二甲基-4-新戊酰氧基-3（2H）-呋喃酮（HDMF新戊酸酯）在使用培养大鼠晶状体的半乳糖诱导模型（体外）中对白内障发展发挥了显著的保护作用。在ICR/f白内障模型（体内）上进行测试时，HDMF新戊酸酯比母体化合物HDMF对白内障发展的抑制作用更显著。该衍生物比HDMF更具亲脂性，因此HDMF新戊酸酯比HDMF更容易穿透角膜。用HDMF新戊酸酯处理的ICR/f大鼠晶状体中观察到HDMF这一事实支持了由HDMF新戊酸酯转化而来的HDMF对白内障发展的抑制作用。
