摘要
目的筛选细胞凋亡相关疾病中重要靶点——卡斯帕酶-3抑制剂。方法利用自建的快速、高效、高通量的卡斯帕酶-3抑制剂的筛选方法,从数千株菌株中筛选阳性菌株。阳性菌株的发酵产物进行分离纯化获得活性化合物,再通过对活性化合物的紫外、质谱、核磁等理化数据的分析进行结构鉴定。结果筛选得到一个活性化合物F03ZA-673A。该化合物对卡斯帕酶-3有较强的抑制活性,IC50=21.1μmol·L-1,它与L-671,776结构相同。结论F03ZA-673 A为一个活性较强的微生物来源卡斯帕酶-3特异性的抑制剂,该化合物对卡斯帕酶-3的抑制活性未见国内外报道。
Abstract
OBJECTIVE To screen inhibitors of caspase-3,which is a key enzyme responsible for diseases related to cell apoptosis.METHODS A rapid and effective high throughput screening method was established for screening caspase-3 inhibitors from metabolites of microorganisms.Among the thousands of strains,the culture broth with active principle was picked out as candidate.The broth was purified to get an active compound.By the data of UV,MS and NMR,the structure of the compound was determined.RESULTS An active compound named F03ZA-673A was isolated from fungi F03ZA-673.The compound showed strong inhibitor activity against caspase-3 with the IC50 of 21.1 μmol·L-1 and it had the same chemical structure as L-671,776.CONCLUSION F03ZA-673A is reported as a strong specific caspase-3 inhibitor for the first time in this study.
关键词
微生物来源 /
卡斯帕酶-3抑制剂 /
高通量筛选
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Key words
microbial source /
caspase-3 inhibitor /
high throughput screening
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任晓;李韶菁;董悦生;杨峻山;张华;穆栋;路新华;郑智慧;刘梅;贺建功.
微生物来源的卡斯帕酶-3抑制剂F03ZA-673A的研究[J]. 中国药学杂志, 2007, 42(12): 907-909
REN Xio;LI Sho-jing;DONG Yue-sheng;YNG Jun-shn;ZHNG Hu;MU Dong;LU Xin-hu;ZHENG Zhi-hui;LIU Mei;HE Jin-gong.
Study on F03ZA-673A,a Caspase-3 Inhibitor from Metabolites of Microorganisms [J]. Chinese Pharmaceutical Journal, 2007, 42(12): 907-909
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脚注
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