Zinc Complexes Developed as Metallopharmaceutics for Treating Diabetes Mellitus based on the Bio-Medicinal Inorganic Chemistry

Yutaka      Yoshikawa; Hiroyuki      Yasui

doi:10.2174/156802612799078874

Abstract

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.

Keywords: Anti-diabetic zinc complexes, diabetes mellitus, insulin signaling, bioinorganic chemistry, bio-coordination chemistry, medicinal inorganic chemistry, metallopharmaceutics, Biological trace metals, platinum drugs, orally active anti-diabetic, anti-metabolic syndrome zinc complexes, target molecule, hydrolysis