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Determination of the inhibition profiles of pyrazolyl–thiazole derivatives against aldose reductase and α‐glycosidase and molecular docking studies      
Yazarlar
Yeliz Demir
Ardahan Üniversitesi, Türkiye
Parham Taslimi
Türkiye
Ümit Muhammet Koçyiğit
Sivas Cumhuriyet Üniversitesi, Türkiye
Musa Akkuş
Türkiye
Muhammet Serhat Özaslan
Ardahan Üniversitesi, Türkiye
Doç. Dr. Hatice Esra DURAN Doç. Dr. Hatice Esra DURAN
Kafkas Üniversitesi, Türkiye
Yakup Budak
Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Burak Tüzün
Sivas Cumhuriyet Üniversitesi, Türkiye
Meliha Burcu Gürdere
Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Mustafa Ceylan
Tokat Gaziosmanpaşa Üniversitesi, Türkiye
Seyithan Taysı
Gaziantep Üniversitesi, Türkiye
İlhami Gülçin
Atatürk Üniversitesi, Türkiye
Şükrü Beydemir
Anadolu Üniversitesi, Türkiye
Özet
Aldose reductase (AR) is the first and rate-limiting enzyme of the polyol pathway, which converts glucose to sorbitol in an NADPH-dependent reaction. α-Glycosidase breaks down starch and disaccharides to glucose. Hence, inhibition of these enzymes can be regarded a considerable approach in the treatment of diabetic complications. AR was purified from sheep liver using simple chromatographic methods. The inhibitory effects of pyrazolyl-thiazoles ((3aR,4S,7R,7aS)-2-(4-{1-[4-(4-bromophenyl)thiazol-2-yl]-5-(aryl)-4,5-dihydro-1H-pyrazol-3-yl}phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives; 3a-i) on AR and α-glycosidase enzymes were investigated. All compounds showed a good inhibitory action against AR and α-glycosidase. Among these compounds, compound 3d exhibited the best inhibition profiles against AR, with a K value of 7.09 ± 0.19 µM, whereas compound 3e showed the lowest inhibition effects, with a K value of 21.89 ± 1.87 µM. Also, all compounds showed efficient inhibition profiles against α-glycosidase, with K values in the range of 0.43 ± 0.06 to 2.30 ± 0.48 µM, whereas the K value of acarbose was 12.60 ± 0.78 µM. Lastly, molecular modeling approaches were implemented to predict the binding affinities of compounds against AR and α-glycosidase. In addition, the ADME analysis of the molecules was performed.
Anahtar Kelimeler
aldose reductase | enzyme inhibition | molecular docking | pyrazolyl-thiazole | alpha-glycosidase
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı ARCHIV DER PHARMAZIE
Dergi ISSN 0365-6233
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q2
Makale Dili İngilizce
Basım Tarihi 12-2020
Cilt No 353
Sayı 12
Sayfalar 2000118 / 0
Doi Numarası 10.1002/ardp.202000118
Makale Linki http://dx.doi.org/10.1002/ardp.202000118