Current landscape and therapeutic prospects of indole-azole hybrids for colorectal cancer treatment: A mini-review.

Colorectal cancer (CRC), which arises from colonic and rectal epithelial tissues, is one of the most common and life-threatening gastrointestinal malignancies worldwide, and its initiation and progression are closely associated with genetic mutations and dysregulated oncogenic signaling pathways. Despite significant advancements in conventional chemotherapy and targeted therapeutic strategies, the clinical management of CRC remains challenged by high metastatic rates, intrinsic or acquired drug resistance, and poor prognosis in patients with advanced-stage disease, underscoring the urgent need to explore novel therapeutic modalities. Indole-azole hybrids have emerged as promising lead compounds for CRC therapy, attributed to their unique dual-scaffold architecture that enables the concurrent targeting of multiple CRC-related oncogenic pathways. This structural synergy not only potentiates their antiproliferative and pro-apoptotic activities against CRC cells but also circumvents the limitations of single-target agents, including narrow therapeutic windows and rapid development of drug resistance. Focusing on the period from 2021 to the present, this review summarizes the state-of-the-art advances in indole-azole hybrids with anti-CRC therapeutic potential. It further elaborates on their structure-activity relationships (SARs), the underlying molecular mechanisms of action, and molecular docking studies, thereby providing novel insights to accelerate the development of innovative therapeutic agents for CRC.