Can İlkay, Çıkrıkcı Kübra, Gençer Nahit, Uslu Harun
Department of Dermatology, Faculty of Medicine, Balikesir University, Balikesir, Türkiye.
Department of Chemistry, Faculty of Art and Science, Balikesir University, Balikesir, Türkiye.
J Enzyme Inhib Med Chem. 2025 Dec;40(1):2540935. doi: 10.1080/14756366.2025.2540935. Epub 2025 Aug 5.
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.
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)