Wagih Nardin, Abdel-Rahman Islam M, El-Koussi Nawal A, El-Din A Abuo-Rahma Gamal
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University New Minia 61111 Egypt
Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University 71526 Assiut Egypt.
RSC Adv. 2025 Jan 13;15(2):966-1010. doi: 10.1039/d4ra05014b. eCollection 2025 Jan 9.
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.
癌症是全球发病和死亡的主要原因之一。癌症发生和发展的主要原因之一是表观遗传失调,这是一种可遗传的修饰,可在不改变DNA序列的情况下改变基因表达。因此,针对这些表观遗传变化已成为一种有前景的治疗策略。苯并咪唑衍生物因其与各种表观遗传靶点相互作用而具有强大的表观遗传调节作用而受到关注,这些靶点包括DNA甲基转移酶、组蛋白脱乙酰酶和组蛋白甲基转移酶。本综述全面概述了抑制不同乙酰化和甲基化读取器、写入器和擦除器表观遗传靶点的苯并咪唑衍生物。在此,我们强调这些化合物在开发靶向性、低毒性癌症治疗方法方面的治疗潜力。目前,一些有前景的苯并咪唑衍生物已进入临床试验,并在血液学和实体恶性肿瘤治疗领域取得了重大进展。因此,我们强调苯并咪唑作为表观遗传药物研究的最新进展,这可能为设计新的多靶点药物以克服耐药性和改善癌症患者的临床结局铺平道路。本综述可帮助研究人员设计出性能更好的新型抗癌苯并咪唑衍生物。