From Rings to Remedies: Investigating the Structure-Activity Relationship of Macrocyclic Anticancer Agents

The profound pharmacological attributes of macrocyclic compounds have spurred their transformation into pharmaceutical drugs. Within conformationally pre-organized ring structures, the macrocycle’s intricate functions and stereochemical complexity contribute to a heightened affinity and selectivity for protein targets. Simultaneously, they maintain sufficient bioavailability to penetrate intracellular locations. As a result, the construction of macrocycles emerges as an optimal strategy for addressing the challenge of “undruggable” targets like cancer. Cancer stands as the second most prevalent and formidable threat to human life, prompting researchers to channel their efforts toward the extraction and synthesis of effective therapeutic drugs designed on macrocyles to combat various types of cancer cells. Many macrocyclic drugs have been licensed by the Food and Drug Administration (FDA) for the treatment of cancer patients. Nonetheless, the significance of these compounds in the production of cancer therapeutics is still undervalued. According to recent research, macrocyclic compounds can be a useful tactic in the fight against drug resistance in the treatment of cancer. This chapter aims to present bits of evidence about the uses of macrocyclic compounds as potential cancer treatments. By providing more innovative approaches to aid cancer patients and society as a whole, this chapter will hopefully stimulate greater interest in the development of macrocyclic medicines for cancer therapy.