A comprehensive review on the role of acetamido as a linker for the design and discovery of anticancer agents.

Cancer is the most significant health problem for mankind, causing millions of deaths every year. After the discovery of chemotherapy, conventional treatments have rapidly developed drug resistance, which has led to the search for novel and more effective anticancer agents. Different linkers have played a crucial role in the design of drugs due to their improved selectivity, physicochemical properties, and therapeutic efficacy. Among these linkers, the acetamido linker has emerged as a promising strategic pathway for enhancing the anticancer potency of drug candidates. Introducing an acetamido linker into the molecular scaffold strategically enhances the pharmacokinetics, stability, and selectivity of anticancer drugs, thus making it more precisely targeted to tumor cells. Acetamido groups have been reported to modulate the interaction between the drug and its molecular targets, enhancing cytotoxicity against a range of cancer cell lines, including different cancer traits. This review discusses the emerging role of acetamido linkers in anticancer drug design, focusing on SAR analysis and their therapeutic effects based on IC₅₀ values against various enzymes and human cancer cell lines. It also provides valuable insights into molecule target interactions, optimisation of various scaffolds for developing safer, more potent, and targeted anticancer therapeutics and an insight into the mechanistic role of acetamido linkers in drug-target interaction. This review underpins the key role of the acetamido linker in the development of new anticancer agents.