Diarylmethanon, bromophenol and diarylmethane compounds: Discovery of potent aldose reductase, alpha-amylase and alpha-glycosidase inhibitors as new therapeutic approach in diabetes and functional hyperglycemia
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, cilt.119, ss.857-863, 2018 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 119
- Basım Tarihi: 2018
- Doi Numarası: 10.1016/j.ijbiomac.2018.08.004
- Dergi Adı: INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.857-863
- Anahtar Kelimeler: alpha-Amylase, alpha-Glycosidase, Aldose reductase, Bromophenols, Diarylmethanons, GRAPE SKIN PHENOLICS, GLUCOSIDASE INHIBITORS, ANTIOXIDANT ACTIVITY, CARBONIC-ANHYDRASE, TANNIC-ACID, DERIVATIVES, METABOLISM, BUTYRYLCHOLINESTERASE, ACETYLCHOLINESTERASE, IDENTIFICATION
- Atatürk Üniversitesi Adresli: Evet
Özet
Diabetes mellitus (DM) is a chronic metabolic disease in which there are high blood sugar levels over a prolonged period. Aldose reductase (AR) belongs to aldo-keto reductase superfamily and plays a key role in the polyol pathway. alpha-Glycosidase and alpha-amylase are important enzymes in glucose metabolism. In this study, AR was purified from purified from cow liver. The enzyme was obtained with 139.17 purification fold and with a specific activity of 1.67 EU/mg protein. Then, it is observed the inhibition effect of diarylmethanons (1a-d), bromophenols (2a-d and 4a-d) and diarylmethanes (3a-d) on aldose reductase, a-glycosidase and alpha-amylase enzymes. In these series, compound 2a showed lowest inhibitory activity against AR with a K-i value of 1.09 +/- 0.29 mu M while compound 2d showed highest inhibitory activity against AR with a K-i value of 0.092 +/- 0.015 mu M. Additionally, alpha-glycosidase and alpha-amylase enzymes were easily inhibited by these compounds. All compounds were tested for their inhibition effects against of alpha-glycosidase enzyme and demonstrated efficient inhibition profiles with K-i values in the range of 14.44 +/- 0.88-43.53 +/- 9.06 nM, and IC50 values in the range of 11.72-46.11 nM. Also, inhibition of the alpha-amylase enzyme, which determined an effective inhibition profile with IC50 values, is in the range of 3.84-29.61 nM. (C) 2018 Elsevier B.V. All rights reserved.