CAJ | 학술논문

目的：分离鉴定链霉菌I06A-03304发酵液中具血管内皮细胞生长因子受体-2胞内酪氨酸激酶(VEGFR2-CD)抑制活性的次生代谢产物。方法采用大孔吸附树脂、羟丙基葡聚糖凝胶(Sephadex LH-20)、C-18反相色谱(ODS)、高压液相色谱(HPLC)等分离手段对次生代谢产物进行分离纯化；通过二级质谱(ESI+-MS2)、紫外光谱(UV)、红外光谱(IR)、核磁共振波谱(NMR)对其结构进行鉴定，以酶联免疫吸附试验(ELISA)法检测其次生代谢产物对VEGFR2-CD的抑制活性。结果分离得到两个二酮哌嗪类化合物院3304A和3304C；化合物3304A的化学结构与环(脯氨酸-亮氨酸)一致，化合物3304C的化学结构与环(脯氨酸-苯丙氨酸)一致，均对VEGFR2-CD表现出一定的抑制活性。结论化合物3304A和3304C是具有VEGFR2-CD抑制活性的二酮哌嗪类次生代谢产物，并为本研究首次报道。
목적：분리감정련매균I06A-03304발효액중구혈관내피세포생장인자수체-2포내락안산격매(VEGFR2-CD)억제활성적차생대사산물。방법채용대공흡부수지、간병기포취당응효(Sephadex LH-20)、C-18반상색보(ODS)、고압액상색보(HPLC)등분리수단대차생대사산물진행분리순화；통과이급질보(ESI+-MS2)、자외광보(UV)、홍외광보(IR)、핵자공진파보(NMR)대기결구진행감정，이매련면역흡부시험(ELISA)법검측기차생대사산물대VEGFR2-CD적억제활성。결과분리득도량개이동고진류화합물원3304A화3304C；화합물3304A적화학결구여배(포안산-량안산)일치，화합물3304C적화학결구여배(포안산-분병안산)일치，균대VEGFR2-CD표현출일정적억제활성。결론화합물3304A화3304C시구유VEGFR2-CD억제활성적이동고진류차생대사산물，병위본연구수차보도。
Objective To discover antagonists of VEGFR2-CD from the fermentation broth produced by streptomyces strain I06A-03304. Methods Under guidance of ELISA assay against VEGFR2-CD, compounds 3304A and 3304C were isolated and purified by HP-20 absorption resin, Sephadex LH-20 gel, ODS reversed-phase chromatography and semi-preparative HPLC. The structures of compounds 3304A and 3304C were identified by combination of analysis of UV, IR, ESI+-MS2 and NMR. Results Compounds 3304A and 3304C were purified and structurally identified as dike-topiperazines, and were the same with cyclo-(Pro-Leu) and cyclo-(Pro-Phe) respectively. Compounds 3304A and 3304C showed weak antagonistic activity against VEGFR2-CD by ELISA assay. Conclusion For the first time, it is re-ported diketopiperazine compounds 3304A and 3304 C have antagonistic activity against VEGFR2-CD.