New inhibitors of aldose reductase: anti-oximes of aromatic aldehydes.
New inhibitors of aldose reductase: anti-oximes of aromatic aldehydes.
复制标题
新型醛糖还原酶抑制剂：芳香醛抗肟类药物。
DOI：
10.1016/0003-9861(91)90086-x
复制
发表时间：
1991
影响因子：
3.9
通讯作者：
Sigman,DS
中科院分区：
文献类型：
--
作者：
Shen,C;Sigman,DS
醛糖还原酶是一种依赖NADPH的酶，催化葡萄糖还原为山梨醇。特定的有效的醛糖还原酶抑制剂具有潜在的药理学用途，因为这种酶在晶状体、周围神经、视网膜和肾小球中产生的山梨醇水平升高可能是慢性糖尿病相关的发病机制。芳香醛类化合物(如苯甲醛和4-氟苯甲醛)已被证明是有效的醛糖还原酶抑制剂，可与目前用于体内抑制该酶的药物相媲美。以苯甲醇为可氧化底物的抑制动力学模式表明，这种抑制是由于形成了由醛糖还原酶、NADP+和抗氧化剂组成的稳定的三元络合物。在马肝乙醇脱氢酶的活性部位形成类似的三元络合物，该酶也被有效底物的抗氧化剂抑制。
Aldose reductase is an NADPH-dependent enzyme which catalyzes the reduction of glucose to sorbitol. Specific potent inhibitors of aldose reductase are of potential pharmacological use because elevated levels of sorbitol produced by this enzyme in lens, peripheral nerve, retina, and renal glomeruli may be responsible for the pathogenesis associated with chronic diabetes. These inhibitors could also serve as probes of the mechanism of action of aldose reductase.anti-Oximes of aromatic aldehydes (e.g., benzaldoxime and 4-fluorobenzaldoxime) have proved to be effective inhibitors of aldose reductase rivaling pharmacological agents currently used to inhibit this enzymein vivo. The kinetic patterns of inhibition in which benzyl alcohol is used as the oxidizable substrate suggest that the inhibition is due to the formation of a stable ternary complex composed of aldose reductase, NADP+, and theanti-oxime. Analogous ternary complexes are formed at the active site of horse liver alcohol dehydrogenase which is also inhibited byanti-oximes of efficient substrates.