Five-Membered Heterocyclic Hybrids as Promising Anticancer Agents: SAR and Biological Activities (2020–2025)

Abstract One of the major limitations in successful cancer chemotherapy is the emergence of multidrug resistance (MDR), a phenomenon that allows cancer cells to evade the cytotoxic effects of various chemotherapeutic agents, even those with different chemical structures and mechanisms of action. To overcome this challenge, the search for novel and more effective anticancer agents remains a priority. Heterocyclic compounds, particularly those containing five-membered rings such as thiazole, triazole, furan, imidazole, oxazole, and thiophene, have garnered significant attention in recent years due to their diverse biological activities. In this review, we have specifically highlighted recent advances in the design and evaluation of heterocyclic compounds with a focus on their anticancer potential. Owing to their structural versatility, favorable pharmacokinetic profiles, and ability to interact with multiple biological targets, these heterocycles serve as promising scaffolds in drug discovery. In this review, we highlight recent advances from 2020 to the present in the development of five-membered heterocyclic hybrids for cancer treatment. A variety of such hybrids have shown strong anticancer efficacy with lower toxicity, making them attractive candidates for further exploration. This review summarizes their structure–activity relationships and biological evaluations. Overall, the article provides valuable insights for medicinal chemists and researchers engaged in the development of next-generation anticancer agents based on five-membered heterocyclic frameworks.