Indazole Derivatives as Emerging Scaffolds for Anti-Breast Cancer Therapy: Synthesis, Structure-Activity Relationship, and Therapeutic Potential

Breast cancer (BC) is the second most common cause of death in women. Current therapies like hormonal therapy, surgery, radiotherapy, and chemotherapy become ineffective due to severe side effects and multidrug resistance. Therefore, there is an urgent need for the development of more effective and safer anti-BC agents. Among different classes of heterocyclic molecules, indazole-based derivatives have emerged as potent anti-BC agents due to their versatile structural features and wide range of biological targets. Indazole is a benzene-pyrazole fused system with potential biological therapeutic significance. This review provides a detailed overview of recent progress in strategies that have expanded the accessible structural diversity of this scaffold. Moreover, mechanistic insights reveal that indazole derivatives mediate their antitumor effects through multi-target modulation, including the inhibition of key kinases such as EGFR, VEGFR, and CDKs, perturbation of microtubule function, activation of apoptotic pathways, and modulation of hormone receptor-dependent signalling, along with SAR. Collectively, this article is a BC-focused integration of different synthetic approaches, the key molecular targets for therapy, and studies showing which groups are responsible for their anti-BC potential, focusing on the latest research published.