An observational study conducted prospectively in a cancer specialty hospital found that drug-related issues were common among elderly cancer patients

Abstract

High glucose levels are a hallmark of the metabolic condition known as diabetes mellitus and is responsible for a higher number of deaths annually than cancer and AIDS combined. Unfortunately, currently available drugs for diabetes treatment have several drawbacks and limitations, such as hepatotoxicity and cardiovascular toxicity, which limit their use as safe drugs. Therefore, our research aims to develop synthetic compounds as potential antidiabetic agents, particularly new analogues of thiazolidine-2,4-dione (TZD), which are recognised as agonists of Peroxisome Proliferator Activated Receptor- γ (PPAR- γ) and oral insulin-sensitizing drugs that reduce insulin resistance. Materials and Methods: Our research focuses on proper substitution at the C-5 position of thiazolidine-2,4-dione to produce better and more effective antidiabetic compounds with improved pharmacological properties and reduced toxicity. We created a number of thiazolidine-2,4-dione analogues with a C-5 substitution and confirmed their structures using IR, 1H-NMR, and MASS spectroscopy. Results: Among the synthesized compounds, three analogues, namely 5-(2-pyridinylbenzylidene) thiazolidine-2,4-dione, 5-(3,4-dimethoxybenzylidene) thiazolidine-2,4-dione, and 5-(2,3,4-trifluorobenzylidene) thiazolidine-2,4-dione, exhibited significant antidiabetic activity in streptozotocin-induced diabetic mice, comparable to the drug Pioglitazone. Molecular docking studies of these compounds using a protein target showed amino acid interactions with Leu270, Gln283, and Arg288, similar to Rosiglitazone and Pioglitazone. Moreover, these compounds did not show any toxic effects in mice, even at a high dose of 2000 mg/kg, indicating their safety profile. Conclusion: The synthesis of modified and improved thiazolidine-2,4-dione-containing drugs, which are safer and more effective than currently available drugs, is of utmost importance in antidiabetic drug research. Our study's findings provide a promising foundation for the development of new TZD analogues as potential antidiabetic agents with improved pharmacological properties and reduced toxicity.