期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 15, 期 14, 页码 4917-4922出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2007.04.062
关键词
insulinomimetic activity; hypoglycemic effect; copper(II)-picolinate complex; type 1 diabetes mellitus
In order to examine the effect of metallopicolinate complexes with first transition metals and develop complexes that are more active than an insulinomimetic leading compound such as oxovanadium(IV)-picolinate complex, VO(pa)(2), 10 metallopicolinate complexes were prepared, and their in vitro insulinomimetic and in vivo antidiabetic activities were evaluated. The in vitro activity was estimated by determining the inhibitory effects of these complexes on free fatty acid release from isolated rat adipocytes treated with epinephrine. Among the complexes, Cu(pa)(2), and Mn(pa)(3) exhibited higher activity than their respective metal ions and better activity than VO(pa)(2). Since Cu(pa)(2) was non-toxic in the cultured rat hepatic M cells, this complex was given streptozotocin (STZ)-induced type 1-like-diabetic mice by single intraperitoneal injection, and found that this complex exhibited a higher hypoglycemic effect than the VG(pa)2 complex. Based on these results, we propose that Cu(pa)2 may be a potent alternative antidiabetic agent. (c) 2007 Elsevier Ltd. All rights reserved.
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