Research Progress on the Anticancer Activity of Natural Indole Alkaloids

Cancer poses a devastating global threat, inflicting immense physical suffering, high mortality rates, severe psychological distress, and substantial economic burdens on individuals, families, and healthcare systems worldwide while gravely compromising quality of life and leaving long-lasting impacts on affected communities. As a fundamental and versatile modality for cancer treatment, chemotherapy exerts a pivotal effect in shrinking tumors, eliminating residual cancer cells, alleviating symptoms, and improving survival rates across various cancer types, whether utilized as monotherapy or in combination with surgery, radiotherapy, or targeted therapies. However, chemotherapy is hampered by several key limitations. The primary drawbacks are tumor cell multidrug resistance, which culminates in impaired drug responsiveness and ultimately treatment failure, and non-specific cytotoxicity, which elicits off-target adverse effects in normal tissues. Accordingly, the development of novel anticancer agents remains an indispensable research priority in contemporary oncology. Natural indole alkaloids, a diverse class of natural secondary metabolites, exhibit notable advantages for cancer therapy, including high target selectivity, multiple anticancer mechanisms, favorable biocompatibility, and ample sources for lead compound discovery. Their structural diversity enables specific binding to cancer-associated molecular targets, while their structural modifiability further optimizes pharmacokinetic profiles, rendering them promising candidates for advancing the development of novel anticancer therapeutics. This review summarizes the recent research progress on natural indole alkaloids with anticancer therapeutic potential, developed over the period 2021 to the present, aiming to provide novel insights for the discovery of innovative anticancer agents.