Hapalindoles from the Cyanobacterium Hapalosiphon sp. Inhibit T Cell Proliferation
Hapalindoles from the Cyanobacterium Hapalosiphon sp. Inhibit T Cell Proliferation
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DOI：
10.1055/a-1045-5178
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发表时间：
2020-01-01
期刊：
影响因子：
2.7
通讯作者：
Gruendemann, Carsten
中科院分区：
文献类型：
--
作者：
Chilczuk, Tomasz;Steinborn, Carmen;Gruendemann, Carsten
目前正在寻找新的免疫调节剂用于治疗自身免疫性疾病和癌症。在这种情况下，575蓝藻提取物的集合的免疫调节作用的筛选活动已经进行。筛选产生了几种活性提取物。在这里，我们报告的结果，随后的研究从蓝藻Hapalosiphon的提取物。CBT 1235。我们确定了5 hapalindoles作为负责观察到的免疫调节作用的化合物。这些吲哚生物碱是由蓝细菌家族Hapalosiphonaceae的几种菌株产生的。它们以其抗感染、细胞毒性和其他生物活性而闻名。人类免疫细胞活性的调节尚未被描述。hapalindoles的免疫调节活性，其特征在于在体外使用基于流式细胞术的测量羧基荧光素二乙酸琥珀酰亚胺酯染色后的T细胞增殖，和膜联蛋白V/碘化丙啶染色后的细胞凋亡和坏死诱导。最有效的化合物，hapalindole A，减少T细胞增殖的IC（50）为1.56 μ M，而相关的凋亡水平仅在10倍高浓度下可测量。Hapalindole A-甲酰胺和hapalindole J-甲酰胺，首次从天然来源中分离，具有比非甲酰化衍生物低得多的活性，同时，抗增殖的选择性低于凋亡作用。
Novel immunomodulating agents are currently sought after for the treatment of autoimmune diseases and cancers. In this context, a screening campaign of a collection of 575 cyanobacteria extracts for immunomodulatory effects has been conducted. The screening resulted in several active extracts. Here we report the results of subsequent studies on an extract from the cyanobacterium Hapalosiphon sp. CBT1235. We identified 5 hapalindoles as the compounds responsible for the observed immunomodulatory effect. These indole alkaloids are produced by several strains of the cyanobacterial family Hapalosiphonaceae. They are known for their anti-infective, cytotoxic, and other bioactivities. Modulation of the activity of human immune cells has not yet been described. The immunomodulatory activity of the hapalindoles was characterized in vitro using flow cytometry-based measurements of T cell proliferation after carboxyfluorescein diacetate succinimidyl ester staining, and apoptosis and necrosis induction after annexin V/propidium iodide staining. The most potent compound, hapalindole A, reduced T cell proliferation with an IC (50) of 1.56 mu M, while relevant levels of apoptosis were measurable only at 10-fold higher concentrations. Hapalindole A-formamide and hapalindole J-formamide, isolated for the first time from a natural source, had much lower activity than the nonformylated derivatives while, at the same time, being less selective for antiproliferative over apoptotic effects.