组蛋白脱乙酰酶抑制剂apicidin及其类似物的抗原虫与抗肿瘤作用研究进展  

Advances of novel HDAC inhibitor apicidin and its analogues as anti-protozoan and anti-neoplastic agents

作　　者：韦进钟[1] 林庆华[2] 谢明权[3] 

机构地区：[1]佛山科学技术学院生命科学学院,南海528231 [2]福建农林大学动物科学学院,福州350002 [3]中山大学生命科学学院,广州510275

出　　处：《中国新药杂志》2005年第2期146-150,共5页Chinese Journal of New Drugs

摘　　要：Apicidin是镰刀菌代谢产物,属环四肽类分子,能结合组蛋白脱乙酰酶(HDAC)使组蛋白过度乙酰化,具有广谱抗顶复亚门原虫和广谱抗肿瘤作用,可抑制肿瘤细胞转移、增殖和促使肿瘤细胞凋亡、分化。对apicidin类似物的生物学活性研究表明,apicidin的癸酸侧链、大环结构和色氨酸侧链是药效基团元件,使其能竞争性结合HDAC,发挥其生物学效应。A novel metabolite of Fusarium spp. apicidin [cyclo (N-O-methyl-L-tryptophanyl- L-isoleucinyl-D-pipecolinyl-L-2-amino-8-oxodecanoyl)], which belongs to the class of cyclic tetrapeptides (CTP), has been recently revealed. Apicidin has the broad-spectral activities against the apicomplexan family of protozoa and tumors by combining with histone deacetylase (HDAC) and making histones hyperacetylated. Apicidin not only inhibits metastasis and proliferation of tumor cells, but also induces apoptosis or differentiation of these cells. Some studies on biological activities of the apicidin analogues demonstrated that the decanoic acid side-chain, macrocyclic structure and Trp side-chain of apicidin are pharmacophore elements that enable this CTP competitively to combine with HDAC. In this review the mechanisms of apicidin as a histone deacetylase inhibitor against protozoa and tumor are discussed, and the significance of its biological efficacy is addressed.

关 键 词：组蛋白脱乙酰酶抑制剂 APICIDIN 抗原虫 抗肿瘤 

分 类 号：R963[医药卫生—微生物与生化药学] R978.61[医药卫生—药理学]