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作为表观遗传靶点抑制剂的抗癌苯并咪唑衍生物：一篇综述文章。

Anticancer benzimidazole derivatives as inhibitors of epigenetic targets: a review article.

作者信息

Wagih Nardin, Abdel-Rahman Islam M, El-Koussi Nawal A, El-Din A Abuo-Rahma Gamal

机构信息

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Deraya University New Minia 61111 Egypt

Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University 71526 Assiut Egypt.

出版信息

RSC Adv. 2025 Jan 13;15(2):966-1010. doi: 10.1039/d4ra05014b. eCollection 2025 Jan 9.

DOI:10.1039/d4ra05014b
PMID:39807197
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11726184/
Abstract

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.

摘要

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。

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Protein lysine acetyltransferase CBP/p300: A promising target for small molecules in cancer treatment.蛋白赖氨酸乙酰转移酶 CBP/p300：癌症治疗中小分子药物的有前途的靶标。
苯并咪唑类：合成子、生物活性先导结构、全合成以及主要生物活性类别的剖析。
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Dual inhibitors of HDAC and other epigenetic regulators: A novel strategy for cancer treatment.双重组蛋白去乙酰化酶和其他表观遗传调节剂抑制剂：癌症治疗的新策略。
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6
Discovery of first novel sigma/HDACi dual-ligands with a potent in vitro antiproliferative activity.发现首个具有强大体外抗增殖活性的新型σ/组蛋白去乙酰化酶抑制剂双配体。
Bioorg Chem. 2023 Nov;140:106794. doi: 10.1016/j.bioorg.2023.106794. Epub 2023 Aug 23.
7
Epigenetic inhibitors and their role in cancer therapy.表观遗传抑制剂及其在癌症治疗中的作用。
Int Rev Cell Mol Biol. 2023;380:211-251. doi: 10.1016/bs.ircmb.2023.04.005. Epub 2023 Aug 1.
8
Concepts, mechanisms and implications of long-term epigenetic inheritance.长期表观遗传遗传的概念、机制和意义。
Curr Opin Genet Dev. 2023 Aug;81:102087. doi: 10.1016/j.gde.2023.102087. Epub 2023 Jul 11.
9
Identification, structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors.苯并咪唑类质子泵抑制剂在电喷雾质谱中常见的吡啶硫氰酸盐中间体的鉴定、结构解析及来源
J Pharm Anal. 2023 Jun;13(6):683-688. doi: 10.1016/j.jpha.2023.04.011. Epub 2023 Apr 21.
10
Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics.癌症化疗及其他：当前状况、候选药物、相关风险以及靶向治疗的进展。
Genes Dis. 2022 Mar 18;10(4):1367-1401. doi: 10.1016/j.gendis.2022.02.007. eCollection 2023 Jul.