Department of Marine Life Sciences, School of Marine Biomedical Sciences, Jeju National University, Jeju 63243, Republic of Korea.
Department of Seafood Science and Technology, Institute of Marine Industry, Gyeongsang National University, Tongyeong 53064, Republic of Korea.
Mar Drugs. 2024 Sep 20;22(9):426. doi: 10.3390/md22090426.
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.
海洋天然产物具有独特的化学结构和广泛的生物活性。本综述旨在总结海洋天然产物海鞘素及其合成类似物的治疗特性和作用机制。海鞘素及其类似物来源于海绵，具有很强的抗肿瘤特性，是癌症治疗的有前途的候选药物。这些化合物具有复杂的分子结构，能够显著抑制微管动力学，导致各种癌细胞系的细胞周期停滞和凋亡。已经发现了几种海鞘素，如海鞘素 B、C、norhalichondrin B 和 homohalichondrin B，它们具有相似的抗癌和抗肿瘤特性。由于天然存在的海鞘素在合成方面存在障碍，最近合成方法的进展使得开发了几种海鞘素类似物成为可能，如 E7389（埃博霉素），它显示出改善的治疗指数。埃博霉素通过多种机制显示出出色的免疫调节特性，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。尽管有很有前景的结果，但这些化合物在合成和临床应用方面仍然存在挑战。本综述探讨了海鞘素及其类似物在癌症治疗中的免疫调节活性的作用机制，以及它们的临床应用和未来药物开发的潜力。
