Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina- ku, Kyoto 607-8414 Japan.
Curr Top Med Chem. 2012;12(3):210-8. doi: 10.2174/156802612799078874.
Biological trace metals such as iron, zinc, copper, and manganese are essential to life and health of humans, and the success of platinum drugs in the cancer chemotherapy has rapidly grown interest in developing inorganic pharmaceutical agents in medicinal chemistry, that is, medicinal inorganic chemistry, using essential elements and other biological trace metals. Transition metal complexes with unique chemical structures may be useful alternatives to the drugs available to address some of the incurable diseases. In this review, we emphasize that metal complexes are an expanding of interest in the research field of treatment of diabetes mellitus. Especially, orally active anti-diabetic and anti-metabolic syndrome zinc complexes have been developed and progressed since the discovery in 2001, where several highly potent anti-diabetic zinc complexes with different coordination structures have quite recently been disclosed, using experimental diabetic animals. In all of the complexes discussed, zinc is found to be biologically active and function by interacting with some target proteins related with diabetes mellitus. The design and screening of zinc complexes with higher activity is not efficient without consideration of the translational research. For the development of a clinically useful metallopharmaceutics, the research of zinc complexes on the long-term toxicity including side effects, clear-cut evidence of target molecule for the in vivo pharmacological action, and good pharmacokinetic property are essential in the current and future studies.
生物微量元素，如铁、锌、铜和锰，对人类的生命和健康是必不可少的，铂类药物在癌症化疗中的成功，迅速激发了人们在药物化学中开发无机药物制剂的兴趣，即药用无机化学，利用必需元素和其他生物微量元素。具有独特化学结构的过渡金属配合物可能是解决一些不治之症的现有药物的有用替代品。在这篇综述中，我们强调金属配合物是治疗糖尿病研究领域日益关注的焦点。特别是，自 2001 年发现以来，具有口服活性的抗糖尿病和抗代谢综合征锌配合物得到了开发和进展，使用实验性糖尿病动物，最近已经披露了几种具有不同配位结构的高活性抗糖尿病锌配合物。在讨论的所有配合物中，锌被发现通过与一些与糖尿病相关的靶蛋白相互作用而具有生物活性和功能。如果不考虑转化研究，设计和筛选具有更高活性的锌配合物的效率不高。为了开发一种临床上有用的金属药物，在当前和未来的研究中，必须研究锌配合物的长期毒性，包括副作用、体内药理作用的明确靶分子证据和良好的药代动力学特性。
