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含吡唑连接磺酰胺部分的塞来昔布衍生物的合成及醛糖还原酶抑制作用。

Synthesis and aldose reductase inhibition effects of celecoxib derivatives containing pyrazole linked-sulfonamide moiety.

机构信息

Dogubayazit Ahmed-i Hani Vocational School, Agri Ibrahim Cecen University, Agri 04400, Turkey; Department of Chemistry, Faculty of Science, Ataturk University, Erzurum 25240, Turkey.

出版信息

Bioorg Chem. 2022 Nov;128:106086. doi: 10.1016/j.bioorg.2022.106086. Epub 2022 Aug 10.

Abstract

In this article, we report the synthesis of Celecoxib derivatives containing the pyrazole-linked sulfonamide moiety. The enzyme inhibition effects of these derivatives on aldose reductase (AR) were also investigated. The IC values of the pyrazole sulfonamide derivatives were determined to be in the range of 40.76-8.25 µM. Among the synthesized derivatives, the compound 16 showed the strongest inhibition effect against the AR enzyme, with an IC value of 8.25 µM. Molecular docking studies were carried out to determine the interactions of the synthesized compounds with the AR enzyme, and ADMET studies were performed to assess the pharmacokinetic and drug-likeness properties.

摘要

在本文中,我们报告了含有吡唑连接的磺酰胺部分的塞来昔布衍生物的合成。还研究了这些衍生物对醛糖还原酶(AR)的酶抑制作用。吡唑磺酰胺衍生物的 IC 值范围在 40.76-8.25 µM 之间。在所合成的衍生物中,化合物 16 对 AR 酶表现出最强的抑制作用,IC 值为 8.25 µM。进行了分子对接研究以确定合成化合物与 AR 酶的相互作用,并进行了 ADMET 研究以评估药代动力学和类药性性质。

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