Indole-pyrimidine hybrids with anticancer therapeutic potential

Indole derivatives constitute a structurally heterogeneous and clinically promising class of anticancer agents. Notably, their biological activity stems from targeting multiple hallmarks of cancer, including dysregulated proliferation, apoptotic evasion, angiogenesis, and epigenetic perturbations, the key processes that drive malignant progression. The indole framework facilitates ready structural modification, enabling specific binding to cancer-selective molecular targets. By comparison, pyrimidine derivatives owe their capacity to act as “molecular mimics” or enzyme inhibitors to their structural analogy to endogenous pyrimidines, which allows them to capitalize on cancer-specific vulnerabilities. Thus, the rational hybridization of indole and pyrimidine scaffolds represents a promising strategy for the development of novel and potent anticancer therapeutics. The present work aims to summarize the current landscape of indole-pyrimidine hybrids with anticancer potential, covering articles published from 2021 to date. The structure-activity relationships and the mechanisms of action are also discussed for further rational design of novel anticancer drug candidates.