真菌来源新活性化合物2460A的研究  

Study of a novel compound 2460A with activities produced by fungus

作　　者：齐小强[1] 朱凤昌 张洋[1] 郭连宏[1] 姜蓉[1] 何琪杨 李元[1] 

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所卫生部抗生素生物工程重点实验室,北京100050

出　　处：《药学学报》2011年第2期165-169,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30371702)

摘　　要：采用自行构建的以重组白细胞介素6受体(IL-6R)为靶位,基于受体配基竞争结合为基础的高通量筛选模型,从微生物代谢产物中获得了新结构化合物2460A。本文通过对产生菌核糖体DNA转录间隔区(rDNA-ITS)序列测定结果,确定了该化合物产生菌为哈茨木霉;研究结果显示,2460A具有和白细胞介素6(IL-6)竞争结合白细胞介素6受体(IL-6R)的活性,因此是具有IL-6R配基活性的微生物产物;MTT法测定结果表明,2460A对CM126和HT-29肿瘤细胞具有抑制作用,IC50分别为2.17×10-5 mol·L-1和1.8×10-5 mol·L-1;对肿瘤细胞周期影响作用实验结果显示,2460A对HT-29细胞的S期略有阻滞作用。本化合物体内抗瘤活性等深入研究工作正在进行中。With IL-6R as target,a new compound 2460A was identified from fungus using HTS screening model.The taxonomics of the produced strain was confirmed to be Trichoderma hazianum rifai after sequencing analysis of rDNA-ITS（internal transcribed spacer）.Results showed that this compound has a binding activity on IL-6R competed with IL-6,thus it is a new ligand of IL-6R originating from microbe.With MTT assay,the anti-tumor activities of 2460A were demonstrated on CM126 and HT-29 cell lines separately,the IC50 are 2.17×10-5 mol·L-1 and 1.8×10-5 mol·L-1 respectively.The compound affected lightly the HT-29 cell cycle at S phase.Studies for the anti-tumor activity of 2460A in vivo are in progress in our lab.

关 键 词：2460A 哈茨木霉 IL-6R配基 抗肿瘤活性 细胞周期 

分 类 号：R965[医药卫生—药理学]