Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications

被引:1
|
作者
Dissanayake, Dinusha Shiromala [1 ]
Nagahawatta, Dineth Pramuditha [1 ]
Lee, Jung-Suck [2 ]
Jeon, You-Jin [1 ]
机构
[1] Jeju Natl Univ, Sch Marine Biomed Sci, Dept Marine Life Sci, Jeju 63243, South Korea
[2] Gyeongsang Natl Univ, Inst Marine Ind, Dept Seafood Sci & Technol, Tongyeong 53064, South Korea
关键词
halichondrin; eribulin; cancer therapeutics; E7389; microtubule disruption; BREAST-CANCER; ERIBULIN MESYLATE; PHASE-I; TUMOR MICROENVIRONMENT; NATURAL-PRODUCTS; B ANALOG; E7389; SUPPRESSES; TRIAL;
D O I
10.3390/md22090426
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
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页数:22
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