2,4-Thiazolidinedione (2,4-TZD), commonly known as glitazone, is a ubiquitous heterocyclic pharmacophore possessing a plethora of pharmacological activities and offering a vast opportunity for structural modification. The diverse range of biological activities endowed with a novel mode of action, low cost, and easy synthesis has attracted the attention of medicinal chemists. Several researchers have integrated the TZD core with different structural fragments to develop a wide range of lead molecules against various clinical disorders. The most common sites for structural modifications at the 2,4-TZD nucleus are the N-3 and the active methylene at C-5. The review covers the recent development of TZD derivatives such as antimicrobial, anticancer, and antidiabetic agents. Various 2,4-TZD based agents or drugs, which are either under clinical development or in the market, are discussed in the study. Different synthetic methodologies for synthesizing the 2,4-TZD core are also included in the manuscript. The importance of various substitutions at N-3 and C-5 and the mechanisms of action and structure-activity relationships are also discussed. We hope this study will serve as a valuable tool for the scientific community engaged in the structural exploitation of the 2,4-TZD core for developing novel drug m\olecules for life-threatening ailments.
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http://dx.doi.org/10.1002/ardp.202100517 | DOI Listing |
Lab Anim
January 2025
Kastamonu University, Faculty of Medicine, Department of Physiology, Kastamonu, Turkey.
Diabetes mellitus, characterized by insufficient insulin secretion and impaired insulin efficacy, disrupts carbohydrate, protein, and lipid metabolism. The global diabetic population is expected to double by 2025, from 380 million, posing a significant health challenge. Most diabetic individuals fall into the type 1 or type 2 categories, and diabetes adversely affects various organs, such as the kidneys, liver, nervous system, reproductive system, and eyes.
View Article and Find Full Text PDFNarra J
December 2024
Department of Histology, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
The most common type of liver cancer is hepatocellular carcinoma (HCC), accounting for 75-85% of cases. Despite its associated side effects, sorafenib remains the standard treatment for HCC. Given the critical need to improve therapeutic efficacy while minimizing adverse effects, alternative drugs must be thoroughly investigated.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Department of Cardiovascular Sciences, College of Life Sciences, University of Leicester, Leicester, UK.
Background: Obesity is a chronic disease associated with increased risk of multiple metabolic and mental health-related comorbidities. Recent advances in obesity pharmacotherapy, particularly with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have the potential to transform obesity and type 2 diabetes mellitus (T2DM) care by promoting marked weight loss, improving glycaemic control and addressing multiple obesity-related comorbidities, with added cardio-renal benefits. Dual agonists combining GLP-1 with other enteropancreatic hormones such as glucose-dependent insulinotropic polypeptide (GIP) have also been developed in recent years, leading to greater weight loss than using GLP-1 RAs alone.
View Article and Find Full Text PDFRev Med Liege
January 2025
Service de Néphrologie, Dialyse, Transplantation, CHU Liège, Belgique.
Chronic kidney disease (CKD) is a common and severe complication in patients with type 2 diabetes (T2D). While inhibitors of the renin-angiotensin system remained for a long time the only medications that had proven nephroprotective effects, several other pharmacological classes also recently showed such a benefit : sodium-glucose cotransporter type 2 (SGLT2) inhibitors (gliflozins), glucagon-like peptide-1 receptor agonists (semaglutide), and mineralocorticoid receptor antagonists (MRA, finerenone). This clinical vignette aims at explaining the pharmacotherapy strategy for a patient with T2D who presents a progressive CKD.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor, Malaysia.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by insulin resistance, leading to elevated blood sugar levels. Exogenous insulin can counteract the diminished response to insulin and effectively controlling blood glucose levels, thereby minimizing diabetes-related complications. However, given the injectable nature of exogenous insulin, apprehensions regarding its safety and the difficulties associated with its administration have hindered its widespread and prompt utilization.
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