Recent Developments in the Discovery of Indole-based Scaffolds as Promising Targeted Cancer Therapeutics

Abstract

Cancer remains a leading cause of mortality worldwide, driving the need for new and more effective therapeutics. Indole-based scaffolds have emerged as highly versatile structural frameworks in drug discovery in view of their structural diversity and ability to modulate multiple biological targets, including kinases, enzymes, and receptors. These compounds exhibit broad anticancer potential by inducing apoptosis, disrupting cell cycle progression, and inhibiting angiogenesis and metastasis. Recent studies highlight small-molecule indoles, bis-indoles, oxindole-based scaffolds, including spirooxindoles, 3-alkenyl oxindoles, 3-iminooxindoles, 4, 5, 6, and 7-azaindole and isoindoline derivatives as promising inhibitors of key cancer pathways, particularly through multi-kinase modulation. However, challenges such as drug resistance, off-target effects, and poor bioavailability must be addressed to fully realize their clinical potential. This review discusses recent progress in the development of indole-related compounds, focusing on their structural features, mechanisms of action, and therapeutic relevance in targeted cancer therapy.