Thiazolidinedione derivatives: emerging role in cancer therapy

Cancer remains the leading cause of death worldwide, with the Globocan 2022 study reporting an estimated 9.7 million cancer deaths. Without the selectivity built for tumour cells, chemotherapeutic agents could be toxic to non-cancerous cells. Administration of such non-selective cytotoxic compounds causes severe side effects and could lead to death. Improved cancer treatments are required to overcome the limitations of the current cancer treatment. The potential of thiazolidinedione derivatives as anticancer drugs has recently drawn attention, despite their primary use as insulin sensitizers in the treatment of type 2 diabetes. The ability of thiazolidinedione derivatives to alter important molecular pathways implicated in carcinogenesis, such as cell proliferation, apoptosis, angiogenesis, Raf kinase, EGFR and HER-2 kinases, HDAC, COX-2 enzyme and metastasis, is highlighted in this review, which examines the growing relevance of these compounds in cancer treatment. Thiazolidinediones have anti-inflammatory, antioxidant, and antiproliferative properties in a variety of cancer types, including breast, colon, and prostate cancers, via activating the peroxisome proliferator-activated gamma receptor (PPARγ). In addition to examining the safety profile and difficulties in clinical translation, the paper looks at preclinical and clinical research that points to these medicines potential to improve the effectiveness of immunotherapy and chemotherapy. This review highlights the encouraging therapeutic possibilities and structure-activity relationship insight of TZDs for their anticancer activity and highlights the molecular level facets of the 'glitazone' pharmacophore for its anticancer activity.

Graphical abstract

TZDs have received immense attention, primarily due to their potential for producing various derivatives. The TZD derivatives activate the PPAR receptor in the apoptosis process, inhibiting crucial enzymes such as histone deacetylase, COX, tyrosine kinases, and Raf kinase.