From Scaffold to Therapy: Benzimidazole Pharmacophore Evolution in Breast Cancer Research

One of the most common malignancies occurring in women worldwide is breast cancer, which highlights the high necessity of new and more efficient therapeutic interventions. Over the last several years, benzimidazole‐based compounds have received much scientific attention because of their wide range of biological activities. The current study offers a detailed discussion of the more recent developments in benzimidazole derivatives for the management of breast cancer with a particular focus on their structure‐activity relationships (SAR), molecular pathobiology, and therapeutic consequences. Recent studies between 2019 and 2025 have shown that benzimidazole derivatives are able to effectively react with a number of key molecular targets, including peptidyl‐prolyl cis‐trans isomerase NIMA‐interacting 1 (Pin1), epidermal growth factor receptor (EGFR), B‐cell lymphoma 2 (Bcl‐2), vascular endothelial growth factor receptor (VEGFR‐2), topoisomerases, tubulin, and histone deacetylases. In such interactions, the compounds trigger apoptosis, cell‐cycle arrest, autophagy, and the generation of oxidative stress in malignant cells‐and usually exhibit minimal toxicity to normal tissues. The present work summarizes recent information about benzimidazole pharmacophores ‐, including their pharmacological targets, SAR, and mechanisms of action, and defines future directions for the development of selective, potent, and clinically viable benzimidazole‐based compounds for the treatment of breast cancer.