کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8305677 1538431 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evaluation of (arene)Ru(II) complexes of curcumin as inhibitors of dipeptidyl peptidase IV
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Evaluation of (arene)Ru(II) complexes of curcumin as inhibitors of dipeptidyl peptidase IV
چکیده انگلیسی
Curcumin, the main component of Curcuma longa, shows an anti-hyperglycemic effect and improved insulin sensitivity. This action may be attributed at least in part to its anti-inflammatory properties and also to its possible interaction with dipeptidyl peptidase-4 (DPPIV), the enzyme that the conversion of glucagon-like peptide-1 (GLP-1), responsible for glucose tolerance into inactive GLP-1. In this work we evaluated the inhibitory activities of a series of different arene-Ru(II)-curcumin complexes on bovine kidney dipeptidyl peptidase-4 (DPPIV). We studied also the interaction of these inhibitors on the enzyme with fluorescence studies displaying the binding poses with molecular docking studies. Specifically organometallic ruthenium(II) complexes of general formula [(η6-arene)Ru(curcuminato)Cl], with arene being p-iPrC6H4Me (1), C6H6 (2), and C6Me6 (3), were evaluated for their inhibition activity toward the mammalian enzyme. Among them, 2 suppressed DPPIV activities more potently (Ki = 20.2(±0.8) μM) than 1, 3, or free curcumin, and all complexes showed an antioxidant activity as free curcumin. As shown from our docking simulations a putative binding site of the compound 2 was found on subdomains S1 and S2 of DPP-IV, where S1 hydrophobic pocket includes catalytic residues and is the primary determinant of substrate specificity for the enzyme. Collectively, our results demonstrate that the complexation of curcumin with ruthenium(II) could be a promising starting point for the development of curcumin-based DPPIV inhibitors.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimie - Volume 99, April 2014, Pages 146-152
نویسندگان
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