近几十年来，表观遗传转录修饰的研究引起了广泛关注。这些过程在许多疾病中起着至关重要的作用，其中包括癌症。组蛋白乙酰转移酶（HAT）和组蛋白去乙酰化酶（HDACs）是参与组蛋白乙酰化和去乙酰化以及最终发生转录后修饰的关键酶。癌症常常表现出表观遗传变化，尤其是HDACs 的表达和活性紊乱。这种紊乱包括调节增殖信号、规避生长抑制物、逃避细胞死亡、促进细胞复制永生、促进血管生成、刺激侵袭和转移、阻止免疫破坏以及基因组不稳定性。大多数肿瘤的发展和扩散都是由于HDAC紊乱导致的。因此，HDAC抑制剂（HDACis）应运而生，现在已经被视为非常有前景的治疗方法。目前，对于几乎所有类型的癌症来说，最为知名和有效的疗法之一是化学治疗。然而，由于其较高的毒性，其治疗效果和安全性受到限制。合成HDACi也存在相同情况。天然产物因其在癌症治疗中相比合成化合物具有的诸多优点，一直以来都是治疗的选择。因此，自然存在的分子对于HDAC抑制剂具有特殊的兴趣，并且由于其潜在的化学结构多样性和生物活性化合物，已引起了研究界的关注。这种多样性为探索毒性更低的HDAC抑制剂以减少与传统合成抑制剂相关的副作用提供了新的途径。本综述详细介绍了天然产物HDACi的机制和生物效应，并对选定的天然HDAC抑制剂及其类似物的结构活性关系进行了简要讨论，以指导未来的研究发现选择性更强、毒性更小的HDACi。© 2023. 作者授权Springer-Verlag GmbH Germany，属于Springer Nature。

The study of epigenetic translational modifications had drawn great interest for the last few decades. These processes play a vital role in many diseases and cancer is one of them. Histone acetyltransferase (HAT) and histone deacetylases (HDACs) are key enzymes involved in the acetylation and deacetylation of histones and ultimately in post-translational modifications. Cancer frequently exhibits epigenetic changes, particularly disruption in the expression and activity of HDACs. It includes the capacity to regulate proliferative signalling, circumvent growth inhibitors, escape cell death, enable replicative immortality, promote angiogenesis, stimulate invasion and metastasis, prevent immunological destruction, and genomic instability. The majority of tumours develop and spread as a result of HDAC dysregulation. As a result, HDAC inhibitors (HDACis) were developed, and they today stand as a very promising therapeutic approach. One of the most well-known and efficient therapies for practically all cancer types is chemotherapy. However, the efficiency and safety of treatment are constrained by higher toxicity. The same has been observed with the synthetic HDACi. Natural products, owing to many advantages over synthetic compounds for cancer treatment have always been a choice for therapy. Hence, naturally available molecules are of particular interest for HDAC inhibition and HDAC has drawn the attention of the research fraternity due to their potential to offer a diverse array of chemical structures and bioactive compounds. This diversity opens up new avenues for exploring less toxic HDAC inhibitors to reduce side effects associated with conventional synthetic inhibitors. The review presents comprehensive details on natural product HDACi, their mechanism of action and their biological effects. Moreover, this review provides a brief discussion on the structure activity relationship of selected natural HDAC inhibitors and their analogues which can guide future research to discover selective, more potent HDACi with minimal toxicity.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.