Identification of new potent inhibitor of aldose reductase from Ocimum basilicum.

Abstract

Recent efforts to develop cure for chronic diabetic complications have led to the discovery of potent inhibitors against aldose reductase (AKR1B1, EC 1.1.1.21) whose role in diabetes is well-evident. In the present work, two new natural products were isolated from the ariel part of Ocimum basilicum; 7-(3-hydroxypropyl)-3-methyl-8-β-O-d-glucoside-2H-chromen-2-one (1) and E-4-(6'-hydroxyhex-3'-en-1-yl)phenyl propionate (2) and confirmed their structures with different spectroscopic techniques including NMR spectroscopy etc. The isolated compounds (1, 2) were evaluated for in vitro inhibitory activity against aldose reductase (AKR1B1) and aldehyde reductase (AKR1A1). The natural product (1) showed better inhibitory activity for AKR1B1 with IC50 value of 2.095±0.77µM compare to standard sorbinil (IC50=3.14±0.02µM). Moreover, the compound (1) also showed multifolds higher activity (IC50=0.783±0.07µM) against AKR1A1 as compared to standard valproic acid (IC50=57.4±0.89µM). However, the natural product (2) showed slightly lower activity for AKR1B1 (IC50=4.324±1.25µM). Moreover, the molecular docking studies of the potent inhibitors were also performed to identify the putative binding modes within the active site of aldose/aldehyde reductases.

• Authors: Huma Aslam Bhatti, Yildiz Tehseen, Kiran Maryam, Maliha Uroos, Bina S Siddiqui, Abdul Hameed, Jamshed Iqbal
• Journal: Bioorganic chemistry (Bioorg Chem) Vol. 75 Pg. 62-70 (12 2017) ISSN: 1090-2120 [Electronic] United States
• PMID: 28917123 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• 7-(3-hydroxypropyl)-3-methyl-8-beta-O-D-glucoside-2H-chromen-2-one
• Benzopyrans
• E-4-(6'-hydroxyhex-3'-en-1-yl)phenylpropionate
• Enzyme Inhibitors
• Glucosides
• Phenylpropionates
• Plant Extracts
• Aldehyde Reductase

Topics

• Aldehyde Reductase (antagonists & inhibitors, metabolism)
• Benzopyrans (chemistry, isolation & purification, metabolism, pharmacology)
• Binding Sites
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (chemistry, isolation & purification, metabolism, pharmacology)
• Glucosides (chemistry, isolation & purification, metabolism, pharmacology)
• Inhibitory Concentration 50
• Magnetic Resonance Spectroscopy
• Molecular Conformation
• Molecular Docking Simulation
• Ocimum basilicum (chemistry, metabolism)
• Phenylpropionates (chemistry, isolation & purification, metabolism, pharmacology)
• Plant Components, Aerial (chemistry, metabolism)
• Plant Extracts (chemistry, pharmacology)
• Protein Structure, Tertiary