吡咯烷类明胶酶抑制剂的合成及初步活性

Synthesis and gelatinase(MMP-2,MMP-9) inhibitory activities of pyrrolidine derivatives

目的设计合成一系列新型吡咯烷衍生物并测定其抑制明胶酶(MMP-2,MMP-9)的活性,研究其构效关系。方法以L-羟脯氨酸为原料,经多步反应合成吡咯烷类衍生物,采用体外抑酶试验测定化合物抑制明胶酶(MMP-2,MMP-9)的活性。结果合成了33个未见文献报道的吡咯烷衍生物,其结构经红外光谱、核磁共振氢谱及质谱确定。其中化合物A0、A8、A9、A10、B9、C10抑制明胶酶的活性较强。结论吡咯烷类衍生物对明胶酶有较强的抑制活性,有可能抑制肿瘤的发生、发展和转移,值得进一步研究。

Aim To design and synthesize new pyrrolidine derivatives and to test their gelatinase（MMP-2, MMP-9） inhibitory activities in order to investigate their structure-activity relationships. Methods A series of pyrrolidine derivatives were synthesized from L-hydroxyproline, and their gelatinase inhibitory activities were assayed in vitro. Results Thirty-three pyrrolidine derivatives were synthesized and their structures were confirmed by IR, 1H-NMR and MS. Several compounds （A0, A8, A9, A10, B9, C10） exhibited potent gelatinase inhibitory activities. Conclusion Pyrrolidine derivatives show remarkable gelatinase inhibitory activities which could have antitumor activities, and are worthy of further investigation.