title: Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.
abstract: Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors.
authors.affiliation: Department of Biology, College of Science, United Arab Emirates University, PO Box 15551, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Priya
authors.initials: P
authors.lastname: Antony
authors.affiliation: Department of Biology, College of Science, United Arab Emirates University, PO Box 15551, Al Ain, Abu Dhabi, United Arab Emirates.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Vijayan
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000490:Allium / Q000737:chemistry; D020134:Catalytic Domain; D030024:Curcuma / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism / Q000493:pharmacokinetics; D020939:Zingiber officinale / Q000737:chemistry; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D064209:Phytochemicals / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics; D010936:Plant Extracts / Q000737:chemistry*; D011485:Protein Binding; D017365:Spices / Q000032:analysis; D013329:Structure-Activity Relationship; D029910:Trigonella / Q000737:chemistry
chemical_list: D004791:Enzyme Inhibitors; D064209:Phytochemicals; D010936:Plant Extracts; D000449:Aldehyde Reductase