从海洋海绵中分离出的halichondrin的免疫调节作用及其在肿瘤学应用中的合成类似物
Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications
影响因子:5.40000
分区:医学2区 / 药物化学2区 药学2区
发表日期:2024 Sep 20
作者:
Dinusha Shiromala Dissanayake, Dineth Pramuditha Nagahawatta, Jung-Suck Lee, You-Jin Jeon
摘要
海洋天然产品包括独特的化学结构和大量生物活动。这篇综述旨在总结海洋天然产品及其合成类似物及其治疗特性和机制。哈利金丁蛋白及其类似物源自海洋海绵，具有有效的抗肿瘤特性，使其成为有希望的癌症治疗候选者。这些化合物以其复杂的分子结构为特征，在抑制微管动力学方面表现出显着的功效，从而导致各种癌细胞系中的细胞周期停滞和凋亡。已经发现了几种类型的halichondrins B，C，C，Norhalichondrin B和Homohalichondrin B具有相似的抗癌和抗肿瘤特征。由于天然可用的halichondrins在合成中显示出障碍，因此合成方法的最新进展使得能够开发几种halichondrin类似物，例如E7389（Eribulin），这些类似物已显示出改善的治疗指数。通过多种机制（例如重编程肿瘤微环境，促进免疫细胞的浸润和激活以及抑制微管动力学），eribulin已显示出出色的免疫调节特性。尽管结果有希望，但这些化合物的合成和临床应用仍存在挑战。这篇综述探讨了哈利金氏蛋白的免疫调节活性及其在癌症治疗中的类似物以及它们的临床应用以及未来药物开发的潜力。
Abstract
Marine natural products comprise unique chemical structures and vast varieties of biological activities. This review aims to summarize halichondrin, a marine natural product, and its synthetic analogs along with its therapeutic properties and mechanisms. Halichondrin and its analogs, derived from marine sponges, exhibit potent antineoplastic properties, making them promising candidates for cancer therapeutics. These compounds, characterized by their complex molecular structures, have demonstrated significant efficacy in inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis in various cancer cell lines. Several types of halichondrins such as halichondrins B, C, norhalichondrin B, and homohalichondrin B have been discovered with similar anticancer and antitumor characteristics. Since naturally available halichondrins show hurdles in synthesis, recent advancements in synthetic methodologies have enabled the development of several halichondrin analogs, such as E7389 (eribulin), which have shown improved therapeutic indices. Eribulin has shown excellent immunomodulatory properties by several mechanisms such as reprogramming tumor microenvironments, facilitating the infiltration and activation of immune cells, and inhibiting microtubule dynamics. Despite promising results, challenges remain in the synthesis and clinical application of these compounds. This review explores the mechanisms underlying the immunomodulatory activity of halichondrin and its analogs in cancer therapy, along with their clinical applications and potential for future drug development.