海绵分离的Halichondrin及其合成类似物在肿瘤学中的免疫调节作用及机制
Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications
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影响因子:5.4
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
DOI:
10.3390/md22090426
摘要
海洋天然产物具有独特的化学结构和丰富的生物活性。本文综述海洋天然产物Halichondrin及其合成类似物的药理特性及机制。Halichondrin及其类似物，来源于海绵，表现出强大的抗肿瘤效果，是潜在的癌症治疗候选药物。这些化合物具有复杂的分子结构，能显著抑制微管动力学，诱导细胞周期阻滞和凋亡。在已发现的多种Halichondrins中，例如Halichondrins B、C、norhalichondrin B和homohalichondrin B，具有类似的抗癌和抗肿瘤特性。由于天然Halichondrins的合成存在困难，近年来合成方法的进展使得多种类似物得以开发，如E7389（eribulin），显示出更优的治疗指数。Eribulin具有出色的免疫调节作用，通过多种机制实现，包括重塑肿瘤微环境、促进免疫细胞浸润与激活、抑制微管动力学。尽管取得了令人鼓舞的成果，但这些化合物的合成和临床应用仍面临挑战。本文探讨了Halichondrin及其类似物在癌症治疗中的免疫调节机制，以及其临床应用和未来药物开发潜力。
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.