Institute of Bioorganic Chemistry of Uzbekistan Academy of Sciences, Tashkent, Uzbekistan.
Department of Natural Substances Chemistry, National University of Uzbekistan, Tashkent, Uzbekistan.
Drug Dev Res. 2023 Aug;84(5):815-838. doi: 10.1002/ddr.22072. Epub 2023 May 8.
Bufadienolides, naturally found in toad venoms having steroid-like structures, reveal antiproliferative effects at low doses. However, their application as anticancer drugs is strongly prevented by their Na /K -ATPase binding activities. Although several kinds of research were dedicated to moderating their Na /K -ATPase binding activity, still deeper fundamental knowledge is required to bring these findings into medical practice. In this work, we reviewed data related to anticancer activity of bufadienolides such as bufalin, arenobufagin, bufotalin, gamabufotalin, cinobufotalin, and cinobufagin and their derivatives. Bufotoxins, derivatives of bufadienolides containing polar molecules mainly belonging to argininyl residues, are reviewed as well. The established structures of bufotoxins have been compiled into a one-page figure to review their structures. We also highlighted advances in the structure-modification of the structure of compounds in this class. Drug delivery approaches to target these compounds to tumor cells were discussed in one section. The issues related to extraction, identification, and quantification are separated into another section.
蟾毒配基是从蟾蜍毒液中发现的具有甾体结构的物质，其在低剂量下具有抗增殖作用。然而，由于其与 Na+/K+-ATP 酶的结合活性，其作为抗癌药物的应用受到强烈阻碍。尽管已经进行了多种研究来调节其 Na+/K+-ATP 酶的结合活性，但仍需要更深入的基础知识才能将这些发现应用于医学实践。在这项工作中，我们综述了与蟾毒配基（如蟾毒它灵、蟾毒它里定、蟾毒灵、华蟾毒精、脂蟾毒配基和华蟾毒精）及其衍生物的抗癌活性相关的数据。我们还综述了含有极性分子（主要为精氨酸残基）的蟾毒配基衍生物蟾毒它灵。已经将蟾毒它灵的已确定结构编译成一页的图表，以综述其结构。我们还强调了对该类化合物结构修饰的进展。在一节中讨论了将这些化合物靶向肿瘤细胞的药物输送方法。在另一节中，讨论了与提取、鉴定和定量相关的问题。
