Publications (16) View all
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Article: Inhibition of human islet amyloid polypeptide or amylin aggregation by two manganese-salen derivatives.
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ABSTRACT: Aggregation of human islet amyloid polypeptide (IAPP) into pancreatic fibrillar deposits has been postulated to be one of the main contributors to impaired insulin secretion and pancreatic β-cell death in approximately 90% of type 2 diabetic patients. So, compounds that prevent cytotoxic protein/polypeptide self-assembly and amyloidogenesis are considered as novel therapeutic agents against this disease. In this study, using thioflavin-T (ThT) and Anilinonaphthalene-8-sulfonic acid (ANS) fluorescence assays, transmission electron microscopy (TEM) and docking studies, we investigated whether EUK-8 and EUK-134, two salen derivatives with proven antioxidants activities, could interfere with the conversion of synthetic human amylin to its insoluble amyloid form. Spectroscopy and electron microscopy data indicated that incubation of human amylin with either EUK-8 or EUK-134 significantly inhibited amyloid formation at two molar ratios of 1:1 and 5:1 (drugs to protein). In addition, [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay showed that treatment of SK-N-MC cells with the pre-formed fibrils in the presence of compounds at drug-to-protein molar ratios of 1:1 and 5:1, dramatically increased the viability of cells compared to the only fibrils formed-treated SK-N-MC cells. Docking results also demonstrated that the aromatic rings of EUK-8 and EUK-134 interact with the hydrophobic region (23-25) of IAPP via Van der Waals interactions. Based on these results and the proven antioxidant properties of these compounds, it could be concluded that these compounds might provide a novel approach to prevent islet amyloid deposition in ß-cells and provide useful information for developing other novel compounds for the treatment of type 2 diabetes.European journal of pharmacology 03/2013; · 2.59 Impact Factor -
Article: Syntheses and structure-activity relationships of seven manganese-salen derivatives as anti-amyloidogenic and fibril-destabilizing agents against hen egg-white lysozyme aggregation.
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ABSTRACT: Accumulation of intra- and/or extracellular misfolded proteins as amyloid fibrils is a key hallmark in more than 20 amyloid-related diseases. In that respect, blocking or reversing amyloid aggregation via the use of small compounds is considered as two useful approaches in hampering the development of these diseases. In this research, we have studied the ability of different manganese-salen derivatives to inhibit amyloid self-assembly as well as to dissolve amyloid aggregates of hen egg-white lysozyme, as an in vitro model system, with the aim of investigating their structure-activity relationships. By coupling several techniques such as thioflavin T and anilinonaphthalene-8-sulfonic acid fluorescence, congo red absorbance, far-UV circular dichroism, and transmission electron microscopy, we demonstrated that all compounds possessed anti-amyloidogenic activities and were capable of dispersing the fibrillar aggregates. In addition, MTT assay of the treated SK-N-MC cells with the preformed fibrils formed in the presence of compounds at a drug-to-protein molar ratio of 5:1, indicated a significant increase in the viability of cells, compared to the fibrils formed in the absence of each of the compounds. Our spectroscopy, electron microscopy, and cellular studies indicated that EUK-15, with a methoxy group at the para position (group R(5)), had higher activity to either inhibit or disrupt the β-sheet structures relative to other compounds. On the basis of these results, it can be concluded that in addition to aromatic rings of each of the derivatives, the type and position of the side group(s) contribute to lower lysozyme fibril accumulation.Chemical Biology & Drug Design 04/2012; 80(2):227-36. · 2.28 Impact Factor -
Article: Phytochemistry and Medicinal Properties of Teucrium polium L. (Lamiaceae).
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ABSTRACT: Teucrium polium L. (family Lamiaceae) is a wild-growing flowering plant, found abundantly in South-Western Asia, Europe and North Africa. Traditionally, T. polium has been used for different pathological conditions such as gastrointestinal disorders, inflammations, diabetes and rheumatism. In traditional Iranian medicine (TIM), the tea of T. polium is used for treating many diseases such as abdominal pain, indigestion, common cold and type 2 diabetes. Based on this background, many studies have been followed for scientific confirmation of the above-mentioned properties. In this review, 100 articles published from 1970 to 2011 in the area of phytochemistry, pharmacology and toxicology of extracts and compounds isolated from T. polium have been evaluated. During the past 40 years, different classes of compounds have been isolated from various parts of T. polium of which the main groups are terpenoids and flavonoids. It has been found that these compounds possess a broad spectrum of pharmacological effects including antioxidant, anticancer, antiinflammatory, hypoglycemic, hepatoprotective, hypolipidemic, antibacterial and antifungal. The results of data analyses on the chemical, pharmacological and toxicological characteristics of T. polium support the view that this plant has beneficial therapeutic properties. However, further studies to identify the active components and further verify their relevant pharmacological activities are warranted. Copyright © 2012 John Wiley & Sons, Ltd.Phytotherapy Research 02/2012; 26(11):1581-93. · 2.09 Impact Factor -
Article: Anti-amyloidogenic and fibril-destabilizing effects of two manganese-salen derivatives against hen egg-white lysozyme aggregation.
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ABSTRACT: Amyloid depositions of proteins play crucial roles in a wide variety of degenerative disorders called amyloidosis. In the present study, we used hen egg white lysozyme (HEWL), as an in vitro model system, to induce fibrillation under high temperatures and acidic pH conditions, and investigated the inhibitory and disruptive effects of two salen-manganese complexes, namely EUK-8 and EUK-134, with aromatic structures, against fibrilization. Results of this study showed that EUK-8 and EUK-134 in a dose-dependent manner inhibited the HEWL aggregation. Similar results were obtained when these compounds were added to pre-formed amyloid fibrils. Docking results also demonstrated that the aromatic rings of EUK-8 and EUK-134 interact with the hydrophobic region of lysozyme via Van der Waals interactions. Results of MTT assay indicated that addition of pre-formed fibrils treated with EUK-8 and EUK-134 at doses 1:1 and 5:1mM; drug to protein, to SK-N-MC cells significantly increased the viability of cells, compared to the fibril sample alone. Based on these results, it might be concluded that in addition to inherent hydrophobicity associated with the ligand section of each of the derivatives, electron density around the central metal ion of the derivatives contributes to lower lysozyme fibril accumulation.International journal of biological macromolecules 10/2011; 50(1):187-97. · 2.37 Impact Factor -
Article: Salen-Manganase Complexes, EUK-8 and EUK-134, Protect Against Protein and Lipid Oxidative in Neuroblastoma Cells and Rat Liver Homogenates in vitro
Research Journal of Biological Sciences. 01/2011;
