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.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2005年第2期146-150,共5页
Chinese Journal of New Drugs
