Ruthenium compounds as potential therapeutic agents for type 2 diabetes mellitus

Eur J Med Chem. 2021 Mar 5:213:113064. doi: 10.1016/j.ejmech.2020.113064. Epub 2020 Dec 1.

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder which is globally responsible for millions of fatalities per year. Management of T2DM typically involves orally administered anti-hyperglycaemic drugs in conjunction with dietary interventions. However, the current conventional therapy seems to be largely ineffective as patients continue to develop complications such as cardiovascular diseases, blindness and kidney failure. Existing alternative treatment entails the administration of organic therapeutic pharmaceuticals, but these drugs have various side effects such as nausea, headaches, weight gain, respiratory and liver damage. Transition metal complexes have shown promise as anti-diabetic agents owing to their diverse mechanisms of activity. In particular, selected ruthenium compounds have exhibited intriguing biological behaviours as Protein Tyrosine Phosphatase (PTP) 1B and Glycogen Synthase Kinase 3 (GSK-3) inhibitors, as well as aggregation suppressants for the human islet amyloid polypeptide (hIAPP). This focussed review serves as a survey on studies pertaining to ruthenium compounds as metallo-drugs for T2DM. Herein, we also provide perspectives on directions to fully elucidate in vivo functions of this class of potential metallopharmaceuticals. More specifically, there is still a need to investigate the pharmacokinetics of ruthenium drugs in order to establish their biodistribution patterns which will affirm whether these metal complexes are substitutionally inert or serve as pro-drugs. In addition, embedding oral-administered ruthenium complexes into bio-compatible polymers can be a prospective means of enhancing stability during drug delivery.

Keywords: Coordination; Diabetes; Inhibitors; Organoruthenium; Suppressants.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Biocompatible Materials / chemistry
  • Coordination Complexes / administration & dosage
  • Coordination Complexes / chemistry*
  • Coordination Complexes / pharmacokinetics
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Carriers / chemistry
  • Drug Liberation
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics
  • Glycogen Synthase Kinase 3 / antagonists & inhibitors*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / chemistry*
  • Hypoglycemic Agents / pharmacokinetics
  • Islet Amyloid Polypeptide / metabolism
  • Nanostructures / chemistry
  • Polymers / chemistry
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Protein Aggregates
  • Protein Tyrosine Phosphatases / antagonists & inhibitors*
  • Ruthenium Compounds / chemistry*
  • Structure-Activity Relationship
  • Tissue Distribution

Substances

  • Biocompatible Materials
  • Coordination Complexes
  • Drug Carriers
  • Enzyme Inhibitors
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • Polymers
  • Prodrugs
  • Protein Aggregates
  • Ruthenium Compounds
  • Glycogen Synthase Kinase 3
  • Protein Tyrosine Phosphatases