Cancer is one of the leading causes of morbidity and mortality worldwide. One of the primary causes of cancer development and progression is epigenetic dysregulation, which is a heritable modification that alters gene expression without changing the DNA sequence. Therefore, targeting these epigenetic changes has emerged as a promising therapeutic strategy. Benzimidazole derivatives have gained attention for their potent epigenetic modulatory effects as they interact with various epigenetic targets, including DNA methyltransferases, histone deacetylases and histone methyltransferases. This review provides a comprehensive overview of benzimidazole derivatives that inhibit different acetylation and methylation reader, writer and eraser epigenetic targets. Herein, we emphasize the therapeutic potential of these compounds in developing targeted, less toxic cancer therapies. Presently, some promising benzimidazole derivatives have entered clinical trials and shown great advancements in the fields of hematological and solid malignancy therapies. Accordingly, we highlight the recent advancements in benzimidazole research as epigenetic agents that could pave the way for designing new multi-target drugs to overcome resistance and improve clinical outcomes for cancer patients. This review can help researchers in designing new anticancer benzimidazole derivatives with better properties.
This journal is © The Royal Society of Chemistry.