Malik Neeru, Singh Rajesh Kumar
School of Pharmacy, Maharaja Agrasen University Dist Solan Baddi 174103 Himachal Pradesh India.
Department of Pharmaceutical Chemistry, Shivalik College of Pharmacy Dist. Rupnagar Nangal 140126 Punjab India
RSC Med Chem. 2025 May 27. doi: 10.1039/d5md00344j.
2,4-Thiazolidinediones (2,4-TZDs) are a class of heterocyclic compounds traditionally recognized for their antidiabetic activity, particularly as peroxisome proliferator-activated receptor gamma (PPARγ) agonists. However, in recent years, they have emerged as promising anticancer scaffolds due to their ability to influence key molecular pathways involved in tumorigenesis, including cell proliferation, apoptosis, angiogenesis, and metastasis. The structural flexibility of the 2,4-TZD core-especially at the C-5 position-makes it highly amenable to derivatization, offering opportunities to fine-tune bioactivity and selectivity. This review presents a focused evaluation of 2,4-TZD derivatives reported between 2020 and 2024, emphasizing structure-activity relationship (SAR) studies and their implications for anticancer drug design. We discuss how various substituent modifications influence cytotoxic potency and target selectivity. In addition, we explore the molecular mechanisms underlying the anticancer activity of selected 2,4-TZD derivatives, along with an overview of their pharmacological relevance. This compilation aims to serve as a valuable resource for medicinal chemists and drug discovery researchers working on next-generation 2,4-TZDs as targeted anticancer therapeutics.
2,4-噻唑烷二酮类（2,4-TZDs）是一类杂环化合物，传统上因其抗糖尿病活性而闻名，特别是作为过氧化物酶体增殖物激活受体γ（PPARγ）激动剂。然而，近年来，由于它们能够影响肿瘤发生过程中涉及的关键分子途径，包括细胞增殖、凋亡、血管生成和转移，它们已成为有前景的抗癌骨架。2,4-TZD核心结构的灵活性——特别是在C-5位——使其非常适合衍生化，为微调生物活性和选择性提供了机会。本综述重点评估了2020年至2024年间报道的2,4-TZD衍生物，强调了构效关系（SAR）研究及其对抗癌药物设计的意义。我们讨论了各种取代基修饰如何影响细胞毒性效力和靶点选择性。此外，我们探讨了所选2,4-TZD衍生物抗癌活性的分子机制，以及它们的药理学相关性概述。本汇编旨在为致力于将下一代2,4-TZDs作为靶向抗癌治疗药物的药物化学家及药物发现研究人员提供有价值的资源。
