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首页> 外文期刊>Acta Biochimica Polonica >[5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPAR gamma ligand
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[5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPAR gamma ligand

机译：[5-（苄氧基）-1H-吲哚-1-基]乙酸，醛糖还原酶抑制剂和PPARγ配体

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摘要

Based on overlapping structural requirements for both efficient aldose reductase inhibitors and PPAR ligands, [5-(benzyloxy)-1H-indol-1-yl] acetic acid (compound 1) was assessed for inhibition of aldose reductase and ability to interfere with PPAR gamma. Aldose reductase inhibition by 1 was characterized by IC50 in submicromolar and low micromolar range, for rat and human enzyme, respectively. Selectivity in relation to the closely related rat kidney aldehyde reductase was characterized by approx. factor 50. At organ level in isolated rat lenses, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner. To identify crucial interactions within the enzyme binding site, molecular docking simulations were performed. Based on luciferase reporter assays, compound 1 was found to act as a ligand for PPAR gamma, yet with rather low activity. On balance, compound 1 is suggested as a promising lead-like scaffold for agents with the potential to interfere with multiple targets in diabetes.
机译：基于有效醛糖还原酶抑制剂和PPAR配体的重叠结构要求，评估了[5-（苄氧基）-1H-吲哚-1-基]乙酸（化合物1）对醛糖还原酶的抑制作用和干扰PPARγ的能力。 1对醛糖还原酶的抑制作用通过IC50分别在大鼠和人的酶的亚微摩尔和低微摩尔范围内表征。相对于紧密相关的大鼠肾醛还原酶的选择性通过约1μm表征。因子50。在离体大鼠晶状体的器官水平上，化合物1以浓度依赖性方式显着抑制山梨醇的积累。为了鉴定酶结合位点内的关键相互作用，进行了分子对接模拟。根据荧光素酶报告基因分析，发现化合物1充当PPARγ的配体，但活性较低。总体而言，化合物1被认为是一种有前途的铅样支架，可用于可能干扰糖尿病多个靶标的药物。

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