Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Kyoto 607-8414, Japan.
J Inorg Biochem. 2013 Apr;121:10-5. doi: 10.1016/j.jinorgbio.2012.12.008. Epub 2012 Dec 23.
Diabetes mellitus (DM) is a considerably diagnosed metabolic disease and a serious problem worldwide. We prepared various zinc complexes and studied their potential for use as new antidiabetic agents. In this study, we synthesized a seleniferous zinc complex, di(2-selenopyridine-N-oxidato)zinc(II) ([ZPS]) that has a Zn(Se2O2) coordination mode. Analyses of structure-activity relationships between its insulin-like activity and the coordination mode of [ZPS]-related complexes showed that it had high insulin-like activity. Hypoglycemic effects of [ZPS] on type 2 diabetic KK-A(y) mice were exerted at the lowest dose administered (1.25-2.5 mg Zn/kg body weight), unlike previously synthesized zinc complexes. Furthermore, [ZPS] afforded us a new advantage; we were able to investigate the tissue distribution of the ligand by measuring the amount of selenium in the organs of [ZPS]-treated mice. Gastrointestinal absorption and tissue penetration of zinc derived from [ZPS] in ddY mice, which was monitored using an isotope tracer technique, was significantly increased compared to that of ZnCl2. These results suggest that [ZPS] has superior antidiabetic effects compared to previously reported zinc complexes, and is thus a potential novel antidiabetic agent that facilitates the possibility of organoselenium ligands as new metal delivery systems for treating DM.
糖尿病（DM）是一种相当常见的代谢疾病，也是全球范围内的一个严重问题。我们制备了各种锌配合物，并研究了它们作为新型抗糖尿病药物的潜力。在这项研究中，我们合成了一种含硒的锌配合物，二（2-吡啶-N-氧化物）锌（II）([ZPS])，其具有 Zn(Se2O2)配位模式。对其胰岛素样活性与其相关配合物的配位模式之间的构效关系进行分析表明，它具有很高的胰岛素样活性。[ZPS]对 2 型糖尿病 KK-A(y)小鼠的降血糖作用在给药的最低剂量（1.25-2.5 mg Zn/kg 体重）下发挥作用，这与之前合成的锌配合物不同。此外，[ZPS]为我们提供了一个新的优势；我们能够通过测量[ZPS]处理小鼠器官中的硒含量来研究配体的组织分布。用同位素示踪技术监测 ddY 小鼠中来自[ZPS]的锌的胃肠道吸收和组织穿透性明显高于 ZnCl2。这些结果表明，[ZPS]具有比以前报道的锌配合物更好的抗糖尿病作用，因此是一种有潜力的新型抗糖尿病药物，使有机硒配体作为治疗 DM 的新型金属输送系统成为可能。
