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皮肤科中的潜在靶点:23种常见皮肤科药物对人碳酸酐酶同工酶I和II的抑制作用

Hidden targets in dermatology: and inhibitory effects of common 23 dermatologic drugs on human carbonic anhydrase isoenzymes I and II.

作者信息

Can İlkay, Çıkrıkcı Kübra, Gençer Nahit, Uslu Harun

机构信息

Department of Dermatology, Faculty of Medicine, Balikesir University, Balikesir, Türkiye.

Department of Chemistry, Faculty of Art and Science, Balikesir University, Balikesir, Türkiye.

出版信息

J Enzyme Inhib Med Chem. 2025 Dec;40(1):2540935. doi: 10.1080/14756366.2025.2540935. Epub 2025 Aug 5.

Abstract

In this study, we have aimed to determine the and effects of 23 frequently used dermatologic drugs on human carbonic anhydrase I (hCA I) and II (hCA II). The inhibitory effects of the drugs on hCA I and hCA II were determined by esterase methods. The most potent inhibitors were isotretinoin for hCA I (Ki= 5.75 µM) and valaciclovir for hCA II (Ki= 5.74 µM). Ketotifen (Ki= 6.98 µM), pantoprazole (Ki= 7.16 µM) and acyclovir (Ki= 7.31 µM) were also potent inhibitors for hCA I. Isotretinoin (Ki= 6.54 µM), brivudine (Ki= 7.44 µM) and fluconazole (Ki= 7.91 µM) were also potent inhibitors for hCA II. Terbinafine hydrochloride was a weak CA inhibitor for both of these isoenzymes (Ki= 20.58 µM for hCA I and 20.32 µM for hCA I). Therefore, the drug, having a weak CA inhibitory activity, may be preferred primarily in patients with a skin disease compared to the other drugs due to important physiological functions of CAs. Molecular docking studies have shown that acitretin and isotretinoin, in particular, will inhibit hCA I at lower concentrations and have higher docking scores. For hCA II, it was shown that Isotretinoin and Ketotifen would inhibit at lower concentrations and have higher placement scores.

摘要

在本研究中,我们旨在确定23种常用皮肤科药物对人碳酸酐酶I(hCA I)和II(hCA II)的 及 影响。通过酯酶方法测定药物对hCA I和hCA II的抑制作用。对hCA I最有效的抑制剂是异维A酸(Ki = 5.75 μM),对hCA II最有效的抑制剂是伐昔洛韦(Ki = 5.74 μM)。酮替芬(Ki = 6.98 μM)、泮托拉唑(Ki = 7.16 μM)和阿昔洛韦(Ki = 7.31 μM)也是hCA I的有效抑制剂。异维A酸(Ki = 6.54 μM)、溴夫定(Ki = 7.44 μM)和氟康唑(Ki = 7.91 μM)也是hCA II的有效抑制剂。盐酸特比萘芬对这两种同工酶都是弱CA抑制剂(对hCA I的Ki = 20.58 μM,对hCA I的Ki = 20.32 μM)。因此,由于碳酸酐酶具有重要的生理功能,与其他药物相比,这种具有弱CA抑制活性的药物可能主要更适合皮肤病患者。分子对接研究表明,特别是阿维A和异维A酸将在较低浓度下抑制hCA I并具有更高的对接分数。对于hCA II,研究表明异维A酸和酮替芬将在较低浓度下抑制并具有更高的放置分数。 (注:原文中部分内容缺失,已按完整可翻译内容呈现)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8401/12326379/c49cb9040aea/IENZ_A_2540935_F0001_C.jpg

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